1 Differentially regulated genes by the AhR using Ahr-null mice and the AhR-selective ligand, TCDD

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This document serves as a record for the reprisal of the kidney and liver cDNA microarrays from the publication Dioxin-Dependent and Dioxin-Independent Gene Batteries: Comparison of Liver and Kidney in AHR-Null Mice. Boutros et al. evaluated AhR-regulated gene expression with 15-week-old, male, wild-type and Ahr-null C57BL/6J mice gavaged with either a single dose of 1000 µg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or purely corn oil vehicle and sacrificed and harvested liver and kidneys 19 hours post-gavage. I haven not been to locate if the livers and kidneys originated with the same mice (that they are paired); so, I have treated each liver and kidney as arising from separate individual mice. The authors came to the conclusion the AhR and interactions between TCDD and the AhR regulate distinct process depending upon the organ. Additionally, they corroborated biochemical studies illustrating TCDD’s selective binding to the AhR (and I have reproduced below) TCDD, independent of AhR, elicits little to no differential mRNA expression.

For processing and modeling the microarray data, I have tried to follow the appropriate methods section of Boutros’s 2009 paper. The raw affymetrix microarray intensity values from GEO entries GSE15857 (kidney) and GSE15858 (liver) are in the data folder.

In Boutros’s paper, they used (and below I have reproduced) the following linear model in limma: \[Y = Basal + AhR + TCDD + AhR:TCDD\] where \(Y\) refers to a ProbeSet’s expression level (see next paragraph for explanation of what a ProbeSet is), \(Basal\) refers to the basal gene expression of a ProbeSet, \(AhR\) refers to the animal’s Ahr genotype, and \(TCDD\) refers to whether the animals was gavaged with 1000 µg/kg TCDD or vehicle. The final term, \(AhR:TCDD\), refers to an effect on a ProbeSet’s expression level explained by the interaction of TCDD and AhR, which makes sense since TCDD selectively binds and activates the AhR, promoting gene regulation. The linear model was fit separately for each organ’s 45,101 unique ProbeSets and for each organ, kidney and liver. After fitting the model to each Probeset, each coefficient’s p-value (for \(AhR\), \(TCDD\), and \(AhR:TCDD\)) were adjusted by the Benjamanini-Hochberg False Discovery Ratio method. This contrasts with their cited Bayesian-FDR method. Although this leads to differences in the exact number of significantly regulated ProbeSets in the liver and kidney as as response to Ahr genotype or TCDD-AhR interactions, my non-Bayesian approach produces roughly similar results.

To clarify what is a ProbeSet in an affymetrix microarray, it is composed of multiple cDNA sequences with slightly different properties that bind to the same particular gene. ProbeSets, which are specific to a gene, are represented by “[1-9]at" and those, which non-specifically cross-hybridize to non-targeted cDNAs, are represented by "[a-z]at”. Some genes have multiple ProbeSets with some specific and others potentially cross-hybridizing. Usually, they are strongly correlated but not always. Although there are ways people use to narrow down the number and variety of ProbeSets, I have not eliminated any because the effort is not worth the loss of potentially valuable information. For certain genes, non-specific ProbeSets are all that’s there: for example, Cyp1a1, the most highly upregulated ProbeSet in the kidney microarrays of wild-type mice after gavaging with 1000 µg/kg TCDD, has only one ProbeSet and it may potentially cross-hybridize (its id is 1422217_a_at).

1.1 Kidney

I performed the Boutros workflow on the kidney gene expression first.

1.1.1 Metadata pull-down

directory <- paste(parent, "data/GSE15857_RAW", sep = "/")

gset <- GEOquery::getGEO("GSE15857", GSEMatrix =TRUE)
accession <- gset$GSE15857_series_matrix.txt.gz$geo_accession
filename <- paste(accession, ".CEL", sep="")
sex <- gset$GSE15857_series_matrix.txt.gz$`gender:ch1`
tissue <- gset$GSE15857_series_matrix.txt.gz$`tissue:ch1`
Ahr <- gset$GSE15857_series_matrix.txt.gz$`ahr:ch1`
treatment <- gset$GSE15857_series_matrix.txt.gz$`treatment:ch1`
GSE15857_meta <- data.frame(cbind(filename, accession, sex, tissue, Ahr, treatment))

#kable(GSE15857_meta, table.attr = "class=\"striped\"", format = "html")
GSE15857_meta
rownames(GSE15857_meta) <- GSE15857_meta$filename

#fns <- list.celfiles(directory)
#fns %in% GSE15857_meta[, 1] 

1.1.2 Reading in Data and Probe-dependent Normalization

Data <- ReadAffy(filenames = GSE15857_meta$filename,
                 phenoData = GSE15857_meta, celfile.path=directory,
                 compress=F,
                 verbose=T, cdfname = "mouse4302")

#exprs(Data)

eset <- gcrma(Data)

#exprs(eset)

eset_norm <- exprs(eset)

#dim(eset_norm)

1.1.3 Cleaning and FC Calculations

## Bimap interface:
probeID <- mouse4302ACCNUM

# Get the probe identifiers that are mapped to an ACCNUM
mapped_probes <- mappedkeys(probeID)

## Bimap interface:
geneID <- mouse4302GENENAME

# Get the probe identifiers that are mapped to an ACCNUM
mapped_genes <- mappedkeys(geneID)

Symbol <- select(mouse4302.db, keys=mapped_genes, columns = c("SYMBOL"))

eset_norm_wSymbols <-
  eset_norm %>%
  as.data.frame() %>%
  rownames_to_column(var = "PROBEID") %>%
  left_join(Symbol, by = "PROBEID") %>%
  dplyr::select("probeID"=PROBEID, "Symbol"=SYMBOL, everything())

## BiomaRt output - 
#ensembl <- biomaRt::useEnsembl(biomart = "genes",mirror="uswest",dataset = "mmusculus_gene_ensembl")
#saveRDS(ensembl, paste(output, "ensembl.RDS", sep = "/"))
ensembl <- readRDS(paste(output, "ensembl.RDS", sep = "/"))
biomart.output <- biomaRt::getBM(mart = ensembl,
                                 filters = "external_gene_name",
                                 values = eset_norm_wSymbols$Symbol,
                                 attributes =c("external_gene_name","description", "chromosome_name"),
                                 uniqueRows = TRUE)

eset_wGeneMeta <-
  eset_norm_wSymbols %>%
  left_join(biomart.output, by = c("Symbol"="external_gene_name")) %>%
  dplyr::select(probeID, Symbol, description, "chromosome"=chromosome_name, everything()) %>%
  distinct(probeID, .keep_all = T)

GSE15857_metaNoFN <-
  GSE15857_meta %>%
  dplyr::select(-filename)
rownames(GSE15857_metaNoFN) <- c()
sampleInfo <- names(GSE15857_metaNoFN)

colnames(eset_wGeneMeta) <- str_remove(colnames(eset_wGeneMeta), pattern = ".CEL")
probeMeta <- c("probeID", "Symbol", "description", "chromosome")
eset_long_design <-
  eset_wGeneMeta %>%
  pivot_longer(-all_of(probeMeta), names_to = "accession", values_to = "expr") %>%
  left_join(GSE15857_metaNoFN, by = c("accession")) %>%
  dplyr::select(all_of(probeMeta), all_of(sampleInfo), everything())

FC_filtCornOil <-
  eset_long_design %>%
  filter(treatment=="Corn oil") %>%
  group_by(Ahr, probeID) %>%
  summarise(meanExpr = mean(expr)) %>%
  group_by(probeID) %>%
  summarise(FC = meanExpr[Ahr=="wildtype"] - meanExpr[Ahr=="knockout"]) %>%
  arrange(desc(FC)) %>%
  left_join(Symbol, by = c("probeID"="PROBEID")) %>%
  dplyr::select(probeID, "Symbol"=SYMBOL, everything()) %>%
  left_join(biomart.output, by = c("Symbol"="external_gene_name")) %>%
  dplyr::select(probeID, Symbol, description, "chromosome"=chromosome_name, everything())


FC_filtTCDD <-
  eset_long_design %>%
  filter(treatment=="TCDD") %>%
  group_by(Ahr, probeID) %>%
  summarise(meanExpr = mean(expr)) %>%
  group_by(probeID) %>%
  summarise(FC = meanExpr[Ahr=="wildtype"] - meanExpr[Ahr=="knockout"]) %>%
  arrange(desc(FC)) %>%
  left_join(Symbol, by = c("probeID"="PROBEID")) %>%
  dplyr::select(probeID, "Symbol"=SYMBOL, everything()) %>%
  left_join(biomart.output, by = c("Symbol"="external_gene_name")) %>%
  dplyr::select(probeID, Symbol, description, "chromosome"=chromosome_name, everything())


FC_filtWT <-
  eset_long_design %>%
  filter(Ahr == "wildtype") %>%
  group_by(treatment, probeID) %>%
  summarise(meanExpr = mean(expr)) %>%
  group_by(probeID) %>%
  summarise(FC = meanExpr[treatment=="TCDD"] - meanExpr[treatment=="Corn oil"]) %>%
  arrange(desc(FC)) %>%
  left_join(Symbol, by = c("probeID"="PROBEID")) %>%
  dplyr::select(probeID, "Symbol"=SYMBOL, everything()) %>%
  left_join(biomart.output, by = c("Symbol"="external_gene_name")) %>%
  dplyr::select(probeID, Symbol, description, "chromosome"=chromosome_name, everything())
  

FC_filtAhrNull <-
  eset_long_design %>%
  filter(Ahr == "knockout") %>%
  group_by(treatment, probeID) %>%
  summarise(meanExpr = mean(expr)) %>%
  group_by(probeID) %>%
  summarise(FC = meanExpr[treatment=="TCDD"] - meanExpr[treatment=="Corn oil"]) %>%
  arrange(desc(FC)) %>%
  left_join(Symbol, by = c("probeID"="PROBEID")) %>%
  dplyr::select(probeID, "Symbol"=SYMBOL, everything()) %>%
  left_join(biomart.output, by = c("Symbol"="external_gene_name")) %>%
  dplyr::select(probeID, Symbol, description, "chromosome"=chromosome_name, everything())

FC_filtWT_Ahr <- 
  FC_filtWT %>% 
  dplyr::select(probeID, FC) %>%
  mutate(Ahr = "wildtype") %>% 
  dplyr::select(Ahr, probeID, FC)

FC_filtAhrnull_Ahr <- 
  FC_filtAhrNull %>% 
  dplyr::select(probeID, FC) %>%
  mutate(Ahr = "knockout") %>% 
  dplyr::select(Ahr, probeID, FC)

FC_WToverKO <-
  rbind(FC_filtWT_Ahr, FC_filtAhrnull_Ahr) %>%
  group_by(probeID) %>%
  summarise(FC = FC[Ahr == "wildtype"] - FC[Ahr == "knockout"]) %>%
  arrange(desc(FC)) %>%
  left_join(Symbol, by = c("probeID"="PROBEID")) %>%
  dplyr::select(probeID, "Symbol"=SYMBOL, everything()) %>%
  left_join(biomart.output, by = c("Symbol"="external_gene_name")) %>%
  dplyr::select(probeID, Symbol, description, "chromosome"=chromosome_name, everything())

Kidney_FCs_table <- 
  FC_filtWT %>%
  rename("FC"="FC_WT_TCDD") %>%
  left_join(FC_filtAhrNull[, which(names(FC_filtAhrNull) %in% c("probeID", "FC"))], by = "probeID") %>%
  rename("FC"="FC_KO_TCDD") %>%
  left_join(FC_WToverKO[, which(names(FC_WToverKO) %in% c("probeID", "FC"))], by = "probeID") %>%
  rename("FC"="FC_TCDD_WToverKO") %>%
  left_join(FC_filtCornOil[, which(names(FC_filtCornOil) %in% c("probeID", "FC"))], by = "probeID") %>%
  rename("FC"="FC_WToverKO_CornOil") %>%
  left_join(FC_filtTCDD[, which(names(FC_filtTCDD) %in% c("probeID", "FC"))], by = "probeID") %>%
  rename("FC"="FC_WToverKO_TCDD") %>%
  distinct(probeID, .keep_all = TRUE)

#kable(Kidney_FCs_table, digits = 4, table.attr = "class=\"striped\"", format = "html")

1.1.4 Principal Components 1 and 2

Kidney gene expression scores plot of first two Principal Components with squares indicating wildtype Ahr mice and circles indicating knockouts; also, red indicating mice gavaged once with 1000 µg/kg TCDD 19 hours prior to sacrifice and blue indicating a gavage with vehicle (0 µg/kg TCDD).

The kidney gene expression is primarily separated by their Ahr genotype as evident by the first Principal Component. Secondarily, it’s driven by the administration of 1000 µg/kg TCDD or vehicle.

kidney_wide_tr <-
  eset_long_design %>%
  dplyr::select(-Symbol, -Ahr, -treatment, -description, -chromosome, -sex, -tissue) %>%
  pivot_wider(names_from = "probeID", values_from = "expr") %>%
  left_join(GSE15857_metaNoFN, by="accession") %>%
  dplyr::select(all_of(sampleInfo), everything())

#PCA
res.pca <- prcomp(kidney_wide_tr[,6:ncol(kidney_wide_tr)], center = TRUE)

# PCA scores
scores <-
  res.pca %>%
  .[["x"]] %>%
  as.data.frame()

# PCs' percent explained variance
eigenAttributes <- factoextra::get_eig(res.pca)
pc1_pev <- round(eigenAttributes[1,which(names(eigenAttributes) %in% c("variance.percent"))],2)
pc2_pev <- round(eigenAttributes[2,which(names(eigenAttributes) %in% c("variance.percent"))],2)

boundaryMaxPC1 <- res.pca[["x"]] %>% as.data.frame() %>% dplyr::select(PC1) %>% max() + 1
boundaryMinPC1 <- res.pca[["x"]] %>% as.data.frame() %>% dplyr::select(PC1) %>% min() - 1
boundaryMaxPC2 <- res.pca[["x"]] %>% as.data.frame() %>% dplyr::select(PC2) %>% max() + 1
boundaryMinPC2 <- res.pca[["x"]] %>% as.data.frame() %>% dplyr::select(PC2) %>% min() - 1
width <- (boundaryMaxPC1 - boundaryMinPC1) / 2
height <- (boundaryMaxPC2 - boundaryMinPC2) / 2
#pdf(paste(directoryPlots, "Boutros_Microarray_Kidney.pdf", sep = "/"), width = width, height = height)
res.pca[["x"]] %>%
  as.data.frame() %>%
  cbind(kidney_wide_tr[,1:5], .) %>%
  ggplot(aes(x = PC1, y = PC2, fill = treatment)) +
  geom_point(aes(shape = Ahr),size=10, stroke = 2, pch=ifelse(Ahr=="knockout", 21, 22)) +
  geom_hline(yintercept=0, alpha = 0.2) +
  geom_vline(xintercept=0, alpha = 0.2) +
  #ggrepel::geom_text_repel(aes(x = PC1, y = PC2, label = ID)) +
  labs(x=bquote("PC1 ("~.(pc1_pev)~"%)"), y=bquote("PC2 ("~.(pc2_pev)~"%)")) +
  scale_fill_discrete(guide = "none") +
  scale_x_continuous(limits = c(boundaryMinPC1, boundaryMaxPC1)) +
  scale_y_continuous(limits = c(boundaryMinPC2, boundaryMaxPC2)) +
  cowplot::theme_cowplot() +
  theme(legend.position = "bottom", 
        legend.justification = "center")

#dev.off()

1.1.5 Statistical Modeling (limma)

Ahr <- as.factor(Ahr)
treatment <- as.factor(treatment)

design <- model.matrix(~ Ahr + treatment + Ahr:treatment)
fit <- lmFit(eset, design)
fit_eb <- eBayes(fit)

tt_fit_eb_ahr <- 
  topTable(fit_eb, number=nrow(eset_norm), coef=2, adjust="BH") %>% # Ahr 
  mutate(Ahr = ifelse(adj.P.Val <= 0.05, "*", "")) %>%
  dplyr::select(Ahr) %>%
  rownames_to_column(var="probeID")

tt_fit_eb_tcdd <- 
  topTable(fit_eb, number=nrow(eset_norm), coef=3, adjust="BH") %>%# TCDD
  mutate(TCDD = ifelse(adj.P.Val <= 0.05, "*", "")) %>%
  dplyr::select(TCDD) %>%
  rownames_to_column(var="probeID")

tt_fit_eb_interaction <- 
  topTable(fit_eb, number=nrow(eset_norm), coef=4, adjust="BH") %>%# Interaction
  mutate(Interaction = ifelse(adj.P.Val <= 0.05, "*", "")) %>%
  dplyr::select(Interaction) %>%
  rownames_to_column(var="probeID")

sigCombined <- 
  tt_fit_eb_ahr %>%
  left_join(tt_fit_eb_tcdd, by = "probeID") %>%
  left_join(tt_fit_eb_interaction, by = "probeID")

Kidney_FCs_table_final <- 
  Kidney_FCs_table %>%
  left_join(sigCombined, "probeID") 

folder_names <- c("parent", "directoryPlots", "output")
rm(list=ls()[! ls() %in% c("Kidney_FCs_table_final", "ensembl", folder_names)])
saveRDS(Kidney_FCs_table_final, paste(output, "Kidney_FCs_table_final.RDS", sep = "/"))

Kidney_FCs_table_final %>%
  dplyr::select(probeID, Symbol, description, FC_WT_TCDD, FC_WToverKO_CornOil) %>%
  arrange(desc(FC_WT_TCDD)) 

1.2 Liver

Below is a reproduction of the Boutros workflow on the liver cDNA microarrays with the frequentist FDR correction instead of the Bayesian-FDR method.

1.2.1 Metadata pull-down

directory <- paste(parent, "data/GSE15858_RAW", sep = "/")

gset <- GEOquery::getGEO("GSE15858", GSEMatrix =TRUE)
accession <- gset$GSE15858_series_matrix.txt.gz$geo_accession
filename <- paste(accession, ".CEL.gz", sep="")
sex <- gset$GSE15858_series_matrix.txt.gz$`gender:ch1`
tissue <- gset$GSE15858_series_matrix.txt.gz$`tissue:ch1`
Ahr <- gset$GSE15858_series_matrix.txt.gz$`ahr:ch1`
treatment <- gset$GSE15858_series_matrix.txt.gz$`treatment:ch1`
GSE15858_meta <- data.frame(cbind(filename, accession, sex, tissue, Ahr, treatment))

GSE15858_meta
rownames(GSE15858_meta) <- GSE15858_meta$filename

#fns <- list.celfiles(directory)
#fns %in% GSE15858_meta[, 1] 

1.2.2 Reading in Data and Probe-dependent Normalization

Data <- ReadAffy(filenames = GSE15858_meta$filename,
                 phenoData = GSE15858_meta, celfile.path=directory,
                 compress=T,
                 verbose=T, cdfname = "mouse4302")

#exprs(Data)

eset <- gcrma(Data)

#exprs(eset)

eset_norm <- exprs(eset)

#dim(eset_norm)

1.2.3 Cleaning and FC Calculations

## Bimap interface:
probeID <- mouse4302ACCNUM

# Get the probe identifiers that are mapped to an ACCNUM
mapped_probes <- mappedkeys(probeID)

## Bimap interface:
geneID <- mouse4302GENENAME

# Get the probe identifiers that are mapped to an ACCNUM
mapped_genes <- mappedkeys(geneID)

Symbol <- select(mouse4302.db, keys=mapped_genes, columns = c("SYMBOL"))

eset_norm_wSymbols <-
  eset_norm %>%
  as.data.frame() %>%
  rownames_to_column(var = "PROBEID") %>%
  left_join(Symbol, by = "PROBEID") %>%
  dplyr::select("probeID"=PROBEID, "Symbol"=SYMBOL, everything())

## BiomaRt output - 
#ensembl <- biomaRt::useEnsembl(biomart = "genes",mirror="uswest",dataset = "mmusculus_gene_ensembl")
biomart.output <- biomaRt::getBM(mart = ensembl,
                                 filters = "external_gene_name",
                                 values = eset_norm_wSymbols$Symbol,
                                 attributes =c("external_gene_name","description", "chromosome_name"),
                                 uniqueRows = TRUE)


eset_wGeneMeta <-
  eset_norm_wSymbols %>%
  left_join(biomart.output, by = c("Symbol"="external_gene_name")) %>%
  dplyr::select(probeID, Symbol, description, "chromosome"=chromosome_name, everything()) %>%
  distinct()

GSE15858_metaNoFN <-
  GSE15858_meta %>%
  dplyr::select(-filename)
rownames(GSE15858_metaNoFN) <- c()
sampleInfo <- names(GSE15858_metaNoFN)

colnames(eset_wGeneMeta) <- str_remove(colnames(eset_wGeneMeta), pattern = ".CEL.gz")
probeMeta <- c("probeID", "Symbol", "description", "chromosome")
eset_long_design <-
  eset_wGeneMeta %>%
  pivot_longer(-all_of(probeMeta), names_to = "accession", values_to = "expr") %>%
  left_join(GSE15858_metaNoFN, by = c("accession")) %>%
  dplyr::select(all_of(probeMeta), all_of(sampleInfo), everything()) %>%
  distinct()

FC_filtCornOil <-
  eset_long_design %>%
  filter(treatment=="Corn oil") %>%
  group_by(Ahr, probeID) %>%
  summarise(meanExpr = mean(expr)) %>%
  group_by(probeID) %>%
  summarise(FC = meanExpr[Ahr=="wildtype"] - meanExpr[Ahr=="knockout"]) %>%
  arrange(desc(FC)) %>%
  left_join(Symbol, by = c("probeID"="PROBEID")) %>%
  dplyr::select(probeID, "Symbol"=SYMBOL, everything()) %>%
  left_join(biomart.output, by = c("Symbol"="external_gene_name")) %>%
  dplyr::select(probeID, Symbol, description, "chromosome"=chromosome_name, everything())


FC_filtTCDD <-
  eset_long_design %>%
  filter(treatment=="TCDD") %>%
  group_by(Ahr, probeID) %>%
  summarise(meanExpr = mean(expr)) %>%
  group_by(probeID) %>%
  summarise(FC = meanExpr[Ahr=="wildtype"] - meanExpr[Ahr=="knockout"]) %>%
  arrange(desc(FC)) %>%
  left_join(Symbol, by = c("probeID"="PROBEID")) %>%
  dplyr::select(probeID, "Symbol"=SYMBOL, everything()) %>%
  left_join(biomart.output, by = c("Symbol"="external_gene_name")) %>%
  dplyr::select(probeID, Symbol, description, "chromosome"=chromosome_name, everything())

FC_filtWT <-
  eset_long_design %>%
  filter(Ahr == "wildtype") %>%
  group_by(treatment, probeID) %>%
  summarise(meanExpr = mean(expr)) %>%
  group_by(probeID) %>%
  summarise(FC = meanExpr[treatment=="TCDD"] - meanExpr[treatment=="Corn oil"]) %>%
  arrange(desc(FC)) %>%
  left_join(Symbol, by = c("probeID"="PROBEID")) %>%
  dplyr::select(probeID, "Symbol"=SYMBOL, everything()) %>%
  left_join(biomart.output, by = c("Symbol"="external_gene_name")) %>%
  dplyr::select(probeID, Symbol, description, "chromosome"=chromosome_name, everything())
  

FC_filtAhrNull <-
  eset_long_design %>%
  filter(Ahr == "knockout") %>%
  group_by(treatment, probeID) %>%
  summarise(meanExpr = mean(expr)) %>%
  group_by(probeID) %>%
  summarise(FC = meanExpr[treatment=="TCDD"] - meanExpr[treatment=="Corn oil"]) %>%
  arrange(desc(FC)) %>%
  left_join(Symbol, by = c("probeID"="PROBEID")) %>%
  dplyr::select(probeID, "Symbol"=SYMBOL, everything()) %>%
  left_join(biomart.output, by = c("Symbol"="external_gene_name")) %>%
  dplyr::select(probeID, Symbol, description, "chromosome"=chromosome_name, everything())

FC_filtWT_Ahr <- 
  FC_filtWT %>% 
  dplyr::select(probeID, FC) %>%
  mutate(Ahr = "wildtype") %>% 
  dplyr::select(Ahr, probeID, FC)

FC_filtAhrnull_Ahr <- 
  FC_filtAhrNull %>% 
  dplyr::select(probeID, FC) %>%
  mutate(Ahr = "knockout") %>% 
  dplyr::select(Ahr, probeID, FC)

FC_WToverKO <-
  rbind(FC_filtWT_Ahr, FC_filtAhrnull_Ahr) %>%
  group_by(probeID) %>%
  summarise(FC = FC[Ahr == "wildtype"] - FC[Ahr == "knockout"]) %>%
  arrange(desc(FC)) %>%
  left_join(Symbol, by = c("probeID"="PROBEID")) %>%
  dplyr::select(probeID, "Symbol"=SYMBOL, everything()) %>%
  left_join(biomart.output, by = c("Symbol"="external_gene_name")) %>%
  dplyr::select(probeID, Symbol, description, "chromosome"=chromosome_name, everything())

Liver_FCs_table <- 
  FC_filtWT %>%
  rename("FC"="FC_WT_TCDD") %>%
  left_join(FC_filtAhrNull[, which(names(FC_filtAhrNull) %in% c("probeID", "FC"))], by = "probeID") %>%
  rename("FC"="FC_KO_TCDD") %>%
  left_join(FC_WToverKO[, which(names(FC_WToverKO) %in% c("probeID", "FC"))], by = "probeID") %>%
  rename("FC"="FC_TCDD_WToverKO") %>%
  left_join(FC_filtCornOil[, which(names(FC_filtCornOil) %in% c("probeID", "FC"))], by = "probeID") %>%
  rename("FC"="FC_WToverKO_CornOil") %>%
  left_join(FC_filtTCDD[, which(names(FC_filtTCDD) %in% c("probeID", "FC"))], by = "probeID") %>%
  rename("FC"="FC_WToverKO_TCDD") %>%
  distinct(probeID, .keep_all = TRUE)

1.2.4 Principal Components 1 and 2

Kidney gene expression scores plot of first two Principal Components with squares indicating wildtype Ahr mice and circles indicating knockouts; also, red indicating mice gavaged once with 1000 µg/kg TCDD 19 hours prior to sacrifice and blue indicating a gavage with vehicle (0 µg/kg TCDD).

Like the kidney, the liver gene expression is primarily separated by their Ahr genotype as evident by the first Principal Component.

Unlike the kidney, which separated wild-type mice by TCDD dose across the second Principal Component, the first Principal Component also separates the wild-type liver gene expression by TCDD dose and simultaneously fails to separate the Ahr-null mice by the same token. Whether an Ahr-null mouse has been gavaged with 1000 µg/kg TCDD or vehicle, it is more similar to an oppositely-treated Ahr-null mouse than they are to a wild-type mouse treated the same. Additionally, as one might expect, Ahr-null mice are more similar to wild-type mice gavaged with the vehicle than they are to the wild-type mice gavaged with TCDD.

liver_wide_tr <-
  eset_long_design %>%
  dplyr::select(probeID, accession, expr) %>%
  distinct() %>%
  pivot_wider(names_from = "probeID", values_from = "expr") %>%
  left_join(GSE15858_metaNoFN, by="accession") %>%
  dplyr::select(all_of(sampleInfo), everything())

#PCA
res.pca <- prcomp(liver_wide_tr[,6:ncol(liver_wide_tr)], center = TRUE)

# PCA scores
scores <-
  res.pca %>%
  .[["x"]] %>%
  as.data.frame()

# PCs' percent explained variance
eigenAttributes <- factoextra::get_eig(res.pca)
pc1_pev <- round(eigenAttributes[1,which(names(eigenAttributes) %in% c("variance.percent"))],2)
pc2_pev <- round(eigenAttributes[2,which(names(eigenAttributes) %in% c("variance.percent"))],2)

boundaryMaxPC1 <- res.pca[["x"]] %>% as.data.frame() %>% dplyr::select(PC1) %>% max() + 1
boundaryMinPC1 <- res.pca[["x"]] %>% as.data.frame() %>% dplyr::select(PC1) %>% min() - 1
boundaryMaxPC2 <- res.pca[["x"]] %>% as.data.frame() %>% dplyr::select(PC2) %>% max() + 1
boundaryMinPC2 <- res.pca[["x"]] %>% as.data.frame() %>% dplyr::select(PC2) %>% min() - 1
width <- (boundaryMaxPC1 - boundaryMinPC1) / 2
height <- (boundaryMaxPC2 - boundaryMinPC2) / 2
#pdf(paste(directoryPlots, "Boutros_Microarray_Liver.pdf", sep = "/"), width = width/10, height = height/10)
res.pca %>%
  .[["x"]] %>%
  as.data.frame() %>%
  cbind(liver_wide_tr[,1:5], .) %>%
  ggplot(aes(x = PC1, y = PC2, fill = treatment, shape = Ahr)) +
  geom_point(size=10, stroke = 2, pch=ifelse(Ahr=="knockout", 21, 22)) +
  geom_hline(yintercept=0, alpha = 0.2) +
  geom_vline(xintercept=0, alpha = 0.2) +
  #ggrepel::geom_text_repel(aes(x = PC1, y = PC2, label = ID)) +
  labs(x=bquote("PC1 ("~.(pc1_pev)~"%)"), y=bquote("PC2 ("~.(pc2_pev)~"%)")) +
  scale_fill_discrete(guide = "none") +
  scale_x_continuous(limits = c(boundaryMinPC1, boundaryMaxPC1)) +
  scale_y_continuous(limits = c(boundaryMinPC2, boundaryMaxPC2)) +
  cowplot::theme_cowplot() +
  theme(legend.position = "bottom", 
        legend.justification = "center")

#dev.off()

1.2.5 Statistical Modeling (limma)

Ahr <- as.factor(Ahr)
treatment <- as.factor(treatment)

design <- model.matrix(~ Ahr + treatment + Ahr:treatment)
fit <- lmFit(eset, design)
fit_eb <- eBayes(fit)

tt_fit_eb <- 
  topTable(fit_eb, number=nrow(eset_norm), coef=2:4) %>%
  mutate(Ahr = ifelse(Ahrwildtype <= 0.05, "*", ""),
         TCDD = ifelse(treatmentTCDD <= 0.05, "*", ""),
         Interaction = ifelse(Ahrwildtype.treatmentTCDD <= 0.05, "*", "")) %>%
  dplyr::select(Ahr, TCDD, Interaction) %>%
  rownames_to_column(var="probeID")

tt_fit_eb_ahr <- 
  topTable(fit_eb, number=nrow(eset_norm), coef=2, adjust="BH") %>% # Ahr 
  mutate(Ahr = ifelse(adj.P.Val <= 0.05, "*", "")) %>%
  dplyr::select(Ahr) %>%
  rownames_to_column(var="probeID")

tt_fit_eb_tcdd <- 
  topTable(fit_eb, number=nrow(eset_norm), coef=3, adjust="BH") %>%# TCDD
  mutate(TCDD = ifelse(adj.P.Val <= 0.05, "*", "")) %>%
  dplyr::select(TCDD) %>%
  rownames_to_column(var="probeID")

tt_fit_eb_interaction <- 
  topTable(fit_eb, number=nrow(eset_norm), coef=4, adjust="BH") %>%# Interaction
  mutate(Interaction = ifelse(adj.P.Val <= 0.05, "*", "")) %>%
  dplyr::select(Interaction) %>%
  rownames_to_column(var="probeID")

sigCombined <- 
  tt_fit_eb_ahr %>%
  left_join(tt_fit_eb_tcdd, by = "probeID") %>%
  left_join(tt_fit_eb_interaction, by = "probeID")

Liver_FCs_table_final <- 
  Liver_FCs_table %>%
  left_join(sigCombined, "probeID") 

folder_names <- c("parent", "directoryPlots", "output")
rm(list=ls()[! ls() %in% c("Kidney_FCs_table_final", "Liver_FCs_table_final", "ensembl", folder_names)])
saveRDS(Liver_FCs_table_final, paste(output, "Liver_FCs_table_final.RDS", sep = "/"))

Liver_FCs_table_final %>%
  dplyr::select(probeID, Symbol, description, FC_WT_TCDD, FC_WToverKO_CornOil) %>%
  arrange(desc(FC_WT_TCDD)) 

1.3 Comparison of Differential ProbeSets in Kidney and Liver

To compare the number of differentially regulated ProbeSets for the liver and kidney, I have focused on primarily three kinds of significantly different ProbeSets: (1) ProbeSets downregulated in Ahr knockout mice when gavaged with vehicle; (2) those upregulated in wild-type mice gavaged with either TCDD or vehicle and (3) also those downregulated. For (1), the significantly downregulated ProbeSets require a functional Ahr for endogenously-regulated gene expression, independent of TCDD. For (2) and (3), the differential ProbeSets have upregulated or downregulated gene expression as a result of TCDD activation of intact C57BL/6 Ahr alleles.

Generally, as evident by the correlation plots, the kidney and the liver’s significantly expressed genes overlap some but are not highly correlated (Ahr-responive \(r\) = 0.15; TCDD:Ahr \(r\) = 0.27).

In corroboration with the Principal Component scores, the upset plots below show the majority of the differentially expressed ProbeSets occur with respect to the status of the Ahr genotype, especially in the kidney. In each tissue, there is also an expected, large intersection of “Ahr-responsive” ProbeSets with differential ProbeSets up- or downregulated by the interaction of TCDD:AhR. The interaction of TCDD:AhR significantly affects many ProbeSets in both the kidney and liver. Very few ProbeSets are differentially expressed by TCDD alone. Between the liver and the kidney, the liver has more ProbeSets significantly regulated across conditions, which Boutros et al. attribute to the greater sequestration of TCDD in the liver than the kidney.

## Ahr regulated genes with Corn Oil FC Expression Gating
L_Ahr_Up <-
  Liver_FCs_table_final %>%
  filter(Ahr == "*", FC_WToverKO_CornOil < 0) %>%
  distinct(probeID) %>%
  drop_na() %>%
  .$probeID

K_Ahr_Up <-
  Kidney_FCs_table_final %>%
  filter(Ahr == "*", FC_WToverKO_CornOil < 0) %>%
  distinct(probeID) %>%
  drop_na() %>%
  .$probeID

L_Ahr_Down <-
  Liver_FCs_table_final %>%
  filter(Ahr == "*", FC_WToverKO_CornOil > 0) %>%
  distinct(probeID) %>%
  drop_na() %>%
  .$probeID

K_Ahr_Down <-
  Kidney_FCs_table_final %>%
  filter(Ahr == "*", FC_WToverKO_CornOil > 0) %>%
  distinct(probeID) %>%
  drop_na() %>%
  .$probeID

## TCDD-AhR regulated genes with Wildtype FC Expression Gating
L_Interx_Up <-
  Liver_FCs_table_final %>%
  filter(Interaction == "*", FC_WT_TCDD > 0) %>%
  distinct(probeID) %>%
  drop_na() %>%
  .$probeID

K_Interx_Up <-
  Kidney_FCs_table_final %>%
  filter(Interaction == "*", FC_WT_TCDD > 0) %>%
  distinct(probeID) %>%
  drop_na() %>%
  .$probeID

L_Interx_Down <-
  Liver_FCs_table_final %>%
  filter(Interaction == "*", FC_WT_TCDD < 0) %>%
  distinct(probeID) %>%
  drop_na() %>%
  .$probeID

K_Interx_Down <-
  Kidney_FCs_table_final %>%
  filter(Interaction == "*", FC_WT_TCDD < 0) %>%
  distinct(probeID) %>%
  drop_na() %>%
  .$probeID

## combining into list
TissueRegged <- list(L_Ahr_Up, K_Ahr_Up, L_Ahr_Down, K_Ahr_Down, L_Interx_Up, K_Interx_Up, L_Interx_Down, K_Interx_Down)
names(TissueRegged) <- c("Liver Ahr KO Upregulated", "Kidney Ahr KO Upregulated", "Liver Ahr KO Downregulated", "Kidney Ahr KO Downregulated", "Liver TCDD:AhR Upregulated", "Kidney TCDD:AhR Upregulated", "Liver TCDD:AhR Downregulated", "Kidney TCDD:AhR Downregulated")

1.3.1 Magnitude and Percentage Differential ProbeSets in Liver and Kidney

frxn_4302 <- function(x, length.computed=FALSE){
  if (length.computed) {
    
    frxn <- x / 4101
    
  } else {
    
    frxn <- length(x) / 45101
    
  }
  return(frxn)
}

tissueCondDiffMag <-
  lapply(TissueRegged, length) %>%
  do.call(rbind, .) %>%
  as.data.frame() %>%
  rename("V1"="Magnitude") %>%
  rownames_to_column(var="Category") 
  
frxnDiffTissue <- 
  lapply(TissueRegged, frxn_4302) %>%
  do.call(rbind, .) %>%
  as.data.frame() %>%
  rename("V1"="Fraction") %>%
  rownames_to_column(var="Category") %>%
  left_join(tissueCondDiffMag, by = "Category") %>%
  mutate(Tissue = ifelse(str_detect(Category, "Liver"), "Liver", "Kidney"),
         Category = ifelse(str_detect(Category, "Liver"), 
                           str_remove(Category, "Liver "), 
                           str_remove(Category, "Kidney ")),
         `Fold Change` = ifelse(str_detect(Category, "Upregulated"), "Upregulated", "Downregulated"),
         Category = ifelse(str_detect(Category, " Upregulated"), 
                           str_remove(Category, " Upregulated"), 
                           str_remove(Category, " Downregulated")),
         Fraction = paste(round(Fraction, 4) * 100, "%", sep=""),
         Tissue = fct_relevel(Tissue, c("Liver", "Kidney"))) %>%
  dplyr::select(Tissue, Category, `Fold Change`, Magnitude, Fraction) %>%
  arrange(Tissue, Category)

frxnDiffTissue 

1.3.2 Fold-Change of Ahr-regulated ProbeSets across Tissues

This figure is a reproduction of FIG 4. (C) in Boutros et al, 2009. The fold-change refers to the wild-type ProbeSet signal over the Ahr-null ProbeSet signal gavaged with vehicle. The color of the points refers to if a ProbeSet was significant in the Kidney, Liver, both, or neither. To calculate the Spearman’s correlation value between Liver and Kidney gene expression, all of the ProbeSets significantly affected by the Ahr-genotype were filtered and non-significant ProbeSets were not included.

L_AhrReg <-
  Liver_FCs_table_final %>%
  dplyr::select(probeID, "Liver_Ahr"=Ahr, "Liver"=FC_WToverKO_CornOil)

K_AhrReg <-
  Kidney_FCs_table_final %>%
  dplyr::select(probeID, "Kidney_Ahr"=Ahr, "Kidney"=FC_WToverKO_CornOil)

LK_AhrReg <-
  L_AhrReg %>%
  left_join(K_AhrReg, by = "probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by = "probeID") %>%
  mutate(Significance = case_when(
    
    (Liver_Ahr == "*" & Kidney_Ahr == "*") ~ "Both",
    (Liver_Ahr == "*" & Kidney_Ahr == "")  ~ "Liver",
    (Liver_Ahr == ""  & Kidney_Ahr == "*") ~ "Kidney",
    (Liver_Ahr == ""  & Kidney_Ahr == "")  ~ "Neither",
    TRUE                                   ~ "Error")) %>%
  dplyr::select(probeID, Symbol, Significance, Liver, Kidney)

tissueAhrCorr <-
  LK_AhrReg %>%
  filter(Significance != "Neither") %>%
  dplyr::select(Liver, Kidney) %>%
  corrr::correlate(method = "spearman") %>%
  filter(term == "Liver") %>%
  mutate(Kidney = round(Kidney, 4)) %>%
  .$Kidney

xMax <- K_AhrReg %>% dplyr::select(Kidney) %>% max() + 1
xMin <- K_AhrReg %>% dplyr::select(Kidney) %>% min() - 1
yMax <- L_AhrReg %>% dplyr::select(Liver) %>% max() + 1
yMin <- L_AhrReg %>% dplyr::select(Liver) %>% min() - 1
width <- (xMax - xMin) / 2
height <- (yMax - yMin) / 2
SigColors <- c("#56B4E9", "#E69F00", "#CC79A7", "#999999")
#pdf(paste(directoryPlots, "Boutros_Microarrays_LK_sigFCs_Ahr.pdf", sep = "/"), width = width+2, height = height+2)
LK_AhrReg %>%
  ggplot(aes(Kidney, Liver, color=Significance, fill=Significance,
             label = ifelse(Significance == "Both", Symbol, ""))) +
  ggrepel::geom_text_repel(force=10) +
  annotate(geom="text", x=xMax-4, y=yMin+2, label=paste("Spearman's: ", tissueAhrCorr),
           size=6, fontface="bold") +
  geom_hline(yintercept=0, alpha = 0.2) +
  geom_vline(xintercept=0, alpha = 0.2) +
  geom_point(size=5, stroke = 2, alpha = 0.5, pch=21) +
  scale_color_manual(values = SigColors) +
  scale_fill_manual(values = SigColors) +
  geom_hline(yintercept=0, alpha = 0.2) +
  geom_vline(xintercept=0, alpha = 0.2) +
  cowplot::theme_cowplot() +
  theme(legend.position = "bottom", 
        legend.justification = "center")

#dev.off()

1.3.3 Fold-Change of TCDD-AhR-regulated ProbeSets across Tissues

This figure is a reproduction of FIG 4. (D) in Boutros et al, 2009. The fold-change refers to the wild-type ProbeSet signal of wild-type mice gavaged with 1000 µg/kg TCDD over wild-type mice gavaged with vehicle. The color of the points refers to if a ProbeSet was significant in the Kidney, Liver, both, or neither. To calculate the Spearman’s correlation value between Liver and Kidney gene expression, all of the ProbeSets significantly affected by the TCDD-AhR interaction were filtered and non-significant ProbeSets were not included.

L_TCDDAhrReg <-
  Liver_FCs_table_final %>%
  dplyr::select(probeID, "Liver_Interaction"=Interaction, "Liver"=FC_WT_TCDD)

K_TCDDAhrReg <-
  Kidney_FCs_table_final %>%
  dplyr::select(probeID, "Kidney_Interaction"=Interaction, "Kidney"=FC_WT_TCDD)

LK_TCDDAhrReg <-
  L_TCDDAhrReg %>%
  left_join(K_TCDDAhrReg, by = "probeID") %>%
  mutate(Significance = case_when(
    
    (Liver_Interaction == "*" & Kidney_Interaction == "*") ~ "Both",
    (Liver_Interaction == "*" & Kidney_Interaction == "")  ~ "Liver",
    (Liver_Interaction == ""  & Kidney_Interaction == "*") ~ "Kidney",
    (Liver_Interaction == ""  & Kidney_Interaction == "")  ~ "Neither",
    TRUE                                                   ~ "Error"
    
  )) %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by = "probeID") %>%
  dplyr::select(probeID, Symbol, Significance, Liver, Kidney)

tissueTCDDAhrCorr <-
  LK_TCDDAhrReg %>%
  filter(Significance != "Neither") %>%
  dplyr::select(Liver, Kidney) %>%
  corrr::correlate(method = "spearman") %>%
  filter(term == "Liver") %>%
  mutate(Kidney = round(Kidney, 4)) %>%
  .$Kidney

xMax <- K_TCDDAhrReg %>% dplyr::select(Kidney) %>% max() + 1
xMin <- K_TCDDAhrReg %>% dplyr::select(Kidney) %>% min() - 1
yMax <- L_TCDDAhrReg %>% dplyr::select(Liver) %>% max() + 1
yMin <- L_TCDDAhrReg %>% dplyr::select(Liver) %>% min() - 1
width <- (xMax - xMin) / 2
height <- (yMax - yMin) / 2
SigColors <- c("#56B4E9", "#E69F00", "#CC79A7", "#999999")
#pdf(paste(directoryPlots, "Boutros_Microarrays_LK_sigFCs_TCDDAhr.pdf", sep = "/"), width = 8, height = 12)
LK_TCDDAhrReg %>%
  ggplot(aes(Kidney, Liver, color=Significance, fill=Significance,
             label = ifelse(Significance == "Both", Symbol, ""))) +
  ggrepel::geom_text_repel(force=1) +
  geom_hline(yintercept=0, alpha = 0.2) +
  geom_vline(xintercept=0, alpha = 0.2) +
  geom_point(size=5, stroke = 2, alpha = 0.5, pch=21) +
  annotate(geom="text", x=xMax-4, y=yMin+2, label=paste("Spearman's: ", tissueTCDDAhrCorr),
           size=6, fontface="bold") +
  scale_color_manual(values = SigColors) +
  scale_fill_manual(values = SigColors) +
  geom_hline(yintercept=0, alpha = 0.2) +
  geom_vline(xintercept=0, alpha = 0.2) +
  cowplot::theme_cowplot() +
  theme(legend.position = "bottom", 
        legend.justification = "center")

#dev.off()

1.3.4 Similar Differential ProbeSets in Liver across Conditions

listAllLiver <- TissueRegged[c(1,3,5,7)]
upset(fromList(listAllLiver), order.by = "freq")

1.3.5 Similar Differential ProbeSets in Kidney across Conditions

listAllKidney  <- TissueRegged[c(2,4,6,8)]
upset(fromList(listAllKidney), order.by = "freq")

1.3.6 Differential ProbeSets by Ahr Genotype Across Tissues

listAhrBothTissues <- TissueRegged[1:4]
upset(fromList(listAhrBothTissues), order.by = "freq")

1.3.7 Downregulated ProbeSets by Ahr Genotype Across Tissues

listAhrDownBothTissues <- TissueRegged[3:4]
upset(fromList(listAhrDownBothTissues), order.by = "freq")

1.3.8 Upregulated ProbeSets by TCDD-Ahr Interaction Across Tissues

listInterUpBothTissues <- TissueRegged[5:6]
upset(fromList(listInterUpBothTissues), order.by = "freq")

1.3.9 Downregulated ProbeSets by TCDD-Ahr Interaction Across Tissues

listInterDownBothTissues <- TissueRegged[7:8]
upset(fromList(listInterDownBothTissues), order.by = "freq")

1.4 Functional Enrichment Analysis

Using intersecting or differing significant ProbeSets across tissues, we can perform functional enrichment analysis on the corresponding gene symbols to see the pathways associated with significant expression in both the kidney and liver and each separately according to Ahr status and the administration of TCDD or vehicle.

For performing functional enrichment analysis I used the R package gProfiler2.

1.4.1 Grabbing Distinct Gene Symbols by Tissue

i_AhrUp <- intersect(L_Ahr_Up, K_Ahr_Up)
L_d_AhrUp <- setdiff(L_Ahr_Up, K_Ahr_Up)
K_d_AhrUp <- setdiff(K_Ahr_Up, L_Ahr_Up)

i_AhrDown <- intersect(L_Ahr_Down, K_Ahr_Down)
L_d_AhrDown <- setdiff(L_Ahr_Down, K_Ahr_Down)
K_d_AhrDown <- setdiff(K_Ahr_Down, L_Ahr_Down)

i_InterxUp <- intersect(L_Interx_Up, K_Interx_Up)
L_d_InterxUp <- setdiff(L_Interx_Up, K_Interx_Up)
K_d_InterxUp <- setdiff(K_Interx_Up, L_Interx_Up)

i_InterxDown <- intersect(L_Interx_Down, K_Interx_Down)
L_d_InterxDown <- setdiff(L_Interx_Down, K_Interx_Down)
K_d_InterxDown <- setdiff(K_Interx_Down, L_Interx_Down)

Symbols_AhrUp <-
  i_AhrUp  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_L_AhrUp <-
  L_d_AhrUp  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_K_AhrUp <-
  K_d_AhrUp  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

Symbols_AhrDown <-
  i_AhrDown  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_L_AhrDown <-
  L_d_AhrDown  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_K_AhrDown <-
  K_d_AhrDown  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

Symbols_InterxUp <-
  i_InterxUp  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_L_InterxUp <-
  L_d_InterxUp  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_K_InterxUp <-
  K_d_InterxUp  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

Symbols_InterxDown <-
  i_InterxDown  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_L_InterxDown <-
  L_d_InterxDown  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_K_InterxDown <-
  K_d_InterxDown  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

1.4.2 gProfiler2 Functional Enrichment

## Ahr upregulated genes  
AhrUp_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_AhrUp$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Liver Ahr upregulated genes  
AhrUp_L_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_L_AhrUp$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Kidney Ahr upregulated genes 
AhrUp_K_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_K_AhrUp$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Ahr downregulated genes  
AhrDown_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_AhrDown$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Liver Ahr downregulated genes  
AhrDown_L_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_L_AhrDown$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Kidney Ahr downregulated genes 
AhrDown_K_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_K_AhrDown$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Interaction upregulated genes  
InterxUp_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_InterxUp$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Interaction upregulated genes  
InterxUp_L_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_L_InterxUp$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Interaction upregulated genes 
InterxUp_K_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_K_InterxUp$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Interaction downregulated genes  
#InterxDown_PathwayEnrichment <-
#  gprofiler2::gost(query = Symbols_InterxDown$Symbol,
#                   organism = "mmusculus",
#                   correction_method = "fdr")

## Interaction downregulated genes  
InterxDown_L_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_L_InterxDown$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Interaction downregulated genes 
InterxDown_K_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_K_InterxDown$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

1.4.3 Functional Enrichment - Ahr Downregulated

AhrDown_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size)

1.4.4 Functional Enrichment - Liver AhR Downregulated

AhrDown_L_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size)

1.4.5 Functional Enrichment - Kidney AhR Downregulated

AhrDown_K_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size)

1.4.6 Functional Enrichment - TCDD-Ahr Upregulated

InterxUp_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size)

1.4.7 Functional Enrichment - Liver TCDD-Ahr Upregulated

InterxUp_L_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size)

1.4.8 Functional Enrichment - Kidney TCDD-Ahr Upregulated

InterxUp_K_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size)

1.4.9 Functional Enrichment - Liver TCDD-Ahr Downregulated

InterxDown_L_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size)

1.4.10 Functional Enrichment - Kidney TCDD-Ahr Downregulated

InterxDown_K_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size)

1.5 Relevance to Beaumont-HNMR Collaboration

The Boutros et al. microarrays provide a glimpse of the Ahr and TCDD-AhR mediated gene expression in the liver and kidney. In our collaboration with the Stewart lab at Beaumont Health, we have detected a dose-dependent induction of Trimethylamine N-Oxide (TMAO) and glycolate in the urine of mice gavaged every 4 days for 28 days with some dose of TCDD (0 - 30 µg/kg TCDD).

TMAO is formed when Trimethylamine (TMA), a small molecule formed by the gut microbiome, is oxidized by Flavin Monooxygenases (FMOs) and primarily by FMO3. In the Boutros et al. study design (gavaged 1000 µg/kg TCDD or vehicle 19 hours before sacrifice), Fmo3 is significantly induced 66-fold in the liver of wild-type mice treated with TCDD compared to vehicle. Fmo2, which has less TMAO-forming activity, is also significantly induced by TCDD (22-fold); additionally, it is significantly induced in Ahr null mice (1.79-fold), suggesting alternative transcription factors regulating its expression. Abcc4, a known exporter of bile acid from the liver into the bloodstream, which has been shown to export TMAO in vitro, is induced ~ 47-fold in wild-type mouse liver after 28 days of gavaging repeatedly with 30 µg/kg TCDD. However, in the Boutros wild-type livers, Abcc4 is only induced 1.47-fold. After TMAO is exported from the liver, it is cleared in the urine and be filtered by the kidney. In the same study, which showed TMAO is exported by Abcc4, TMAO was shown to be imported into kidney cells by Slc22a2, which in the Boutros kidney microarray is modestly downregulated by TCDD exposure (1.03 fold) similar to Slc47a1 (1.06-fold), which exports TMAO from renal cells. Interestingly, both transporters are downregulated in Ahr-null mice (1.21- and 1.12-fold, respectively) suggesting their expression is partly dependent on AhR-mediated kidney development.

Glycolate is formed from primarily two pathways: hydroxyproline catabolism, which occurs primarily in the liver, and glyoxal detoxification, which occurs in the liver, kidney, and other tissues. Hydroxyproline is an essential building block of collagen and has been previously been shown by Nault et al. to be dose-dependently induced in mice repeatedly gavaged with TCDD to support liver fibrosis. Maybe the most pertinent enzyme in the pathway related to glycolate, Hao1, catalyzes the formation of glyoxylate from glycolate and atmospheric oxygen with Flavin Mononucleotide (FMN). Experiments with KO models of Hao1 or a riboflavin-deficient diet in mice have shown an increase in levels of urinary glycolate levels. It is one of the most dose-dependently reduced enzymes in the liver of male mice repeatedly gavaged for 28 days with 30 µg/kg TCDD (~ 250-fold). In the wild-type livers of Boutros et al., it is more modestly reduced (1.2-fold); although it along with its peroxisomal partner Agxt and the glyoxal detoxifying enzyme Glo1 have significantly altered expression in Ahr-null liver. In the KOs, Hao1 and Glo1 are reduced 1.4 and 2.1-fold, respectively, and Agxt is induced 1.88-fold. In the wild-type kidneys of Boutros et al., Aldh2, which turns glyoxal precursors into glycolate, is induced (1.57-fold).

1.5.1 TMA-TMAO Pathway

L_TMAO_Symbols <- c("Fmo1", "Fmo2", "Fmo3", "Abcc4")
L_TMAO <-
  Liver_FCs_table_final %>%
  filter(Symbol %in% L_TMAO_Symbols) %>%
  mutate(Tissue = "Liver") %>%
  group_by(Symbol) %>%
  slice_max(abs(FC_WT_TCDD), n=1) %>%
  mutate(FC_WT_TCDD = 2**(FC_WT_TCDD),
         FC_WToverKO_CornOil = 2**(FC_WToverKO_CornOil)) %>%
  dplyr::select(Tissue, Symbol, description, "Wild-type FC" = FC_WT_TCDD, "Corn Oil FC" = FC_WToverKO_CornOil,
               Ahr, TCDD, "TCDD:AhR" = Interaction) %>%
  arrange(factor(Symbol, levels = L_TMAO_Symbols))

K_TMAO_Symbols <- c("Slc22a2", "Slc47a1", "Slc22a8")
K_TMAO <-
  Kidney_FCs_table_final %>%
  filter(Symbol %in% K_TMAO_Symbols) %>%
  mutate(Tissue = "Kidney") %>%
  group_by(Symbol) %>%
  slice_max(abs(FC_WT_TCDD), n=1) %>%
  mutate(FC_WT_TCDD = 2**(FC_WT_TCDD),
         FC_WToverKO_CornOil = 2**(FC_WToverKO_CornOil)) %>%
  dplyr::select(Tissue, Symbol, description, "Wild-type FC" = FC_WT_TCDD, "Corn Oil FC" = FC_WToverKO_CornOil,
               Ahr, TCDD, "TCDD:AhR" = Interaction) %>%
  arrange(factor(Symbol, levels = K_TMAO_Symbols))

rbind(L_TMAO, K_TMAO)

1.5.2 Glycolate-producing Enzymes

L_Gly_Symbols <- c("Prodh2", "Aldh4a1", "Got2", "Hoga1", "Grhpr", "Agxt2", "Ldha", "Hao1", "Agxt", "Glo1", "Hagh", "Aldh2")
L_Gly <-
  Liver_FCs_table_final %>%
  filter(Symbol %in% L_Gly_Symbols) %>%
  mutate(Tissue = "Liver") %>%
  group_by(Symbol) %>%
  slice_max(abs(FC_WT_TCDD), n=1) %>%
  mutate(FC_WT_TCDD = 2**(FC_WT_TCDD),
         FC_WToverKO_CornOil = 2**(FC_WToverKO_CornOil)) %>%
  dplyr::select(Tissue, Symbol, description, "Wild-type FC" = FC_WT_TCDD, "Corn Oil FC" = FC_WToverKO_CornOil,
               Ahr, TCDD, "TCDD:AhR" = Interaction) %>%
  arrange(factor(Symbol, levels = L_Gly_Symbols))

K_Gly_Symbols <- c("Glo1", "Hagh", "Aldh2", "Slc26a6")
K_Gly <-
  Kidney_FCs_table_final %>%
  filter(Symbol %in% K_Gly_Symbols) %>%
  mutate(Tissue = "Kidney") %>%
  group_by(Symbol) %>%
  slice_max(abs(FC_WT_TCDD), n=1) %>%
  mutate(FC_WT_TCDD = 2**(FC_WT_TCDD),
         FC_WToverKO_CornOil = 2**(FC_WToverKO_CornOil)) %>%
  dplyr::select(Tissue, Symbol, description, "Wild-type FC" = FC_WT_TCDD, "Corn Oil FC" = FC_WToverKO_CornOil,
               Ahr, TCDD, "TCDD:AhR" = Interaction) %>%
  arrange(factor(Symbol, levels = K_Gly_Symbols))

rbind(L_Gly, K_Gly)

2 Supplemental: Comparison of (FC-agnostic) Differential Probes across Tissue by Ahr Genotype and TCDD-AhR Interaction

2.1 Upset Plots of Significant Genes

sigLivAhr <- Liver_FCs_table_final[Liver_FCs_table_final$Ahr == "*", ]$probeID
sigLivTCDD <- Liver_FCs_table_final[Liver_FCs_table_final$TCDD == "*", ]$probeID
sigLivInterX <- Liver_FCs_table_final[Liver_FCs_table_final$Interaction == "*", ]$probeID

sigKidAhr <- Kidney_FCs_table_final[Kidney_FCs_table_final$Ahr == "*", ]$probeID
sigKidTCDD <- Kidney_FCs_table_final[Kidney_FCs_table_final$TCDD == "*", ]$probeID
sigKidInterX <- Kidney_FCs_table_final[Kidney_FCs_table_final$Interaction == "*", ]$probeID

listOfSigs <- list(sigLivAhr, sigLivTCDD, sigLivInterX, sigKidAhr, sigKidTCDD, sigKidInterX)
names(listOfSigs) <- c("Liver_Ahr", "Liver_TCDD", "Liver_InterX", "Kidney_Ahr", "Kidney_TCDD", "Kidney_InterX")

2.1.1 TCDD-AhR Interaction with Wildtype FC Expression Gating

i_AhrUp <- intersect(L_Ahr_Up, K_Ahr_Up)
L_d_AhrUp <- setdiff(L_Ahr_Up, K_Ahr_Up)
K_d_AhrUp <- setdiff(K_Ahr_Up, L_Ahr_Up)

i_AhrDown <- intersect(L_Ahr_Down, K_Ahr_Down)
L_d_AhrDown <- setdiff(L_Ahr_Down, K_Ahr_Down)
K_d_AhrDown <- setdiff(K_Ahr_Down, L_Ahr_Down)

i_InterxUp <- intersect(L_Interx_Up, K_Interx_Up)
L_d_InterxUp <- setdiff(L_Interx_Up, K_Interx_Up)
K_d_InterxUp <- setdiff(K_Interx_Up, L_Interx_Up)

i_InterxDown <- intersect(L_Interx_Down, K_Interx_Down)
L_d_InterxDown <- setdiff(L_Interx_Down, K_Interx_Down)
K_d_InterxDown <- setdiff(K_Interx_Down, L_Interx_Down)

2.1.2 Grabbing Distinct Gene Symbols by Tissue

Symbols_AhrUp <-
  i_AhrUp  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_L_AhrUp <-
  L_d_AhrUp  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_K_AhrUp <-
  K_d_AhrUp  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

Symbols_AhrDown <-
  i_AhrDown  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_L_AhrDown <-
  L_d_AhrDown  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_K_AhrDown <-
  K_d_AhrDown  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

Symbols_InterxUp <-
  i_InterxUp  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_L_InterxUp <-
  L_d_InterxUp  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_K_InterxUp <-
  K_d_InterxUp  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

Symbols_InterxDown <-
  i_InterxDown  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_L_InterxDown <-
  L_d_InterxDown  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_K_InterxDown <-
  K_d_InterxDown  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

2.1.3 gProfiler2 Functional Enrichment

## Ahr upregulated genes  
AhrUp_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_AhrUp$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Liver Ahr upregulated genes  
AhrUp_L_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_L_AhrUp$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Kidney Ahr upregulated genes 
AhrUp_K_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_K_AhrUp$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Ahr downregulated genes  
AhrDown_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_AhrDown$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Liver Ahr downregulated genes  
AhrDown_L_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_L_AhrDown$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Kidney Ahr downregulated genes 
AhrDown_K_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_K_AhrDown$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Interaction upregulated genes  
InterxUp_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_InterxUp$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Interaction upregulated genes  
InterxUp_L_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_L_InterxUp$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Interaction upregulated genes 
InterxUp_K_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_K_InterxUp$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Interaction downregulated genes  
#InterxDown_PathwayEnrichment <-
#  gprofiler2::gost(query = Symbols_InterxDown$Symbol,
#                   organism = "mmusculus",
#                   correction_method = "fdr")

## Interaction downregulated genes  
InterxDown_L_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_L_InterxDown$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Interaction downregulated genes 
InterxDown_K_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_K_InterxDown$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

2.1.4 In the Liver

listOfSigsLiv <- listOfSigs[1:3]
upset(fromList(listOfSigsLiv), order.by = "freq")

2.1.5 In the Kidney

listOfSigsKid <- listOfSigs[4:6]
upset(fromList(listOfSigsKid), order.by = "freq")

2.1.6 By Ahr Genotype

Altered_Ahr <- listOfSigs[c(1, 4)]
upset(fromList(Altered_Ahr), order.by = "freq")

2.1.7 By Interaction of Genotype and TCDD

Altered_Interaction <- listOfSigs[c(3, 6)]
upset(fromList(Altered_Interaction), order.by = "freq")

2.2 Upset plots of Significant Pathways

2.2.1 Grabbing Distinct Gene Symbols by Tissue

Symbols_sigLivAhr <-
  sigLivAhr  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_sigLivInterX <-
  sigLivInterX  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

Symbols_sigKidAhr <-
  sigKidAhr  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()
  
Symbols_sigKidInterX <-
  sigKidInterX  %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

2.2.2 Grabbing Distinct Gene Symbols by Genotype

names(Altered_Ahr) <- c("L", "K")
i_sigAhr <- intersect(Altered_Ahr[["L"]], Altered_Ahr[["K"]])
L_d_sigAhr <- setdiff(Altered_Ahr[["L"]], Altered_Ahr[["K"]])
K_d_sigAhr <- setdiff(Altered_Ahr[["K"]], Altered_Ahr[["L"]])

Symbols_i_sigAhr <-
  i_sigAhr %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

Symbols_L_d_sigAhr <-
  L_d_sigAhr %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

Symbols_K_d_sigAhr <-
  K_d_sigAhr %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

2.2.3 Grabbing Distinct Gene Symbols by Interaction

names(Altered_Interaction) <- c("L", "K")
i_sigInterx <- intersect(Altered_Interaction[["L"]], Altered_Interaction[["K"]])
L_d_sigInterx <- setdiff(Altered_Interaction[["L"]], Altered_Interaction[["K"]])
K_d_sigInterx <- setdiff(Altered_Interaction[["K"]], Altered_Interaction[["L"]])

Symbols_i_sigInterx <-
  i_sigInterx %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

Symbols_L_d_sigInterx <-
  L_d_sigInterx %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

Symbols_K_d_sigInterx <-
  K_d_sigInterx %>%
  as.data.frame() %>%
  rename("."="probeID") %>%
  left_join(Liver_FCs_table_final[,which(names(Liver_FCs_table_final) %in% c("probeID", "Symbol"))], by="probeID") %>%
  distinct(Symbol) %>%
  drop_na()

2.2.4 gProfiler2 Functional Enrichment

## Liver Ahr genetype and interaction
Liver_Ahr_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_sigLivAhr$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

Liver_Interx_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_sigLivInterX$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Kidney Ahr genetype and interaction
Kidney_Ahr_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_sigKidAhr$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

Kidney_Interx_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_sigKidInterX$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Same Ahr regulated genes across tissue
TissueIntersect_Ahr_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_i_sigAhr$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Diff Ahr regulated genes in liver
Diff_Liver_Ahr_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_L_d_sigAhr$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Diff Ahr regulated genes in kidney
Diff_Kidney_Ahr_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_K_d_sigAhr$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Same TCDD-Ahr regulated genes across tissue
TissueIntersect_Interx_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_i_sigInterx$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Diff TCDD-Ahr regulated genes in liver
Diff_Liver_Interx_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_L_d_sigInterx$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

## Diff TCDD-Ahr regulated genes in kidney
Diff_Kidney_Interx_PathwayEnrichment <-
  gprofiler2::gost(query = Symbols_K_d_sigInterx$Symbol,
                   organism = "mmusculus",
                   correction_method = "fdr")

2.2.5 Functional Enrichment - Liver Ahr Regulated

kable(Liver_Ahr_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size), 
      table.attr = "class=\"striped\"", format = "html")
source term_name term_size intersection_size
GO:BP small molecule metabolic process 1713 131
GO:BP organic acid metabolic process 944 90
GO:BP carboxylic acid metabolic process 896 86
GO:BP oxoacid metabolic process 908 86
GO:BP monocarboxylic acid metabolic process 616 56
GO:BP lipid metabolic process 1344 83
GO:BP small molecule biosynthetic process 617 50
GO:BP cellular amino acid metabolic process 253 32
GO:BP organic acid biosynthetic process 290 34
GO:BP metabolic process 11429 324
GO:BP alpha-amino acid metabolic process 182 27
GO:BP cellular lipid metabolic process 994 64
GO:BP cellular catabolic process 2059 99
GO:BP obsolete oxidation-reduction process 548 45
GO:BP carboxylic acid biosynthetic process 282 32
GO:BP catabolic process 2399 108
GO:BP carboxylic acid catabolic process 221 28
GO:BP organic acid catabolic process 228 28
GO:BP fatty acid metabolic process 425 38
GO:BP small molecule catabolic process 346 34
GO:BP cellular metabolic process 10350 296
GO:BP hormone metabolic process 219 26
GO:BP organonitrogen compound metabolic process 6326 204
GO:BP organic substance catabolic process 1985 89
GO:BP cellular amino acid catabolic process 92 17
GO:BP organic substance metabolic process 10989 303
GO:BP alpha-amino acid catabolic process 80 15
GO:BP cellular modified amino acid metabolic process 179 21
GO:BP regulation of hormone levels 559 38
GO:BP alpha-amino acid biosynthetic process 62 13
GO:BP organic hydroxy compound metabolic process 527 36
GO:BP response to hormone 912 50
GO:BP sulfur compound metabolic process 317 27
GO:BP carbohydrate derivative metabolic process 975 51
GO:BP response to endogenous stimulus 1619 71
GO:BP cellular hormone metabolic process 135 17
GO:BP regulation of biological quality 3876 132
GO:BP organophosphate metabolic process 891 47
GO:BP primary metabolic process 10243 276
GO:BP lipid biosynthetic process 647 38
GO:BP generation of precursor metabolites and energy 446 30
GO:BP response to oxygen-containing compound 1820 74
GO:BP steroid metabolic process 306 24
GO:BP cellular amino acid biosynthetic process 62 11
GO:BP alcohol metabolic process 344 25
GO:BP carbohydrate metabolic process 587 34
GO:BP aromatic amino acid family metabolic process 30 8
GO:BP monocarboxylic acid biosynthetic process 194 18
GO:BP tyrosine metabolic process 14 6
GO:BP organic substance transport 2416 88
GO:BP localization 6168 180
GO:BP acylglycerol metabolic process 143 15
GO:BP cellular response to chemical stimulus 3097 105
GO:BP transport 4502 140
GO:BP neutral lipid metabolic process 145 15
GO:BP nucleobase-containing small molecule metabolic process 537 31
GO:BP establishment of localization 4658 143
GO:BP organonitrogen compound biosynthetic process 1570 63
GO:BP cellular ketone metabolic process 213 18
GO:BP triglyceride metabolic process 112 13
GO:BP liver development 173 16
GO:BP regulation of lipid metabolic process 361 24
GO:BP monosaccharide biosynthetic process 96 12
GO:BP unsaturated fatty acid metabolic process 133 14
GO:BP monosaccharide metabolic process 266 20
GO:BP hepaticobiliary system development 176 16
GO:BP organonitrogen compound catabolic process 1249 53
GO:BP nucleoside phosphate metabolic process 476 28
GO:BP protein catabolic process in the vacuole 18 6
GO:BP response to organonitrogen compound 1093 48
GO:BP drug metabolic process 68 10
GO:BP glutathione metabolic process 70 10
GO:BP response to wounding 517 29
GO:BP response to organic cyclic compound 1043 46
GO:BP cellular amide metabolic process 1077 47
GO:BP regulation of hydrolase activity 1183 50
GO:BP aspartate family amino acid metabolic process 43 8
GO:BP lipid catabolic process 335 22
GO:BP organophosphate biosynthetic process 500 28
GO:BP phosphate-containing compound metabolic process 2809 94
GO:BP dicarboxylic acid metabolic process 92 11
GO:BP response to nitrogen compound 1199 50
GO:BP liver morphogenesis 32 7
GO:BP response to organic substance 3418 109
GO:BP regulation of peptidase activity 480 27
GO:BP positive regulation of lipid metabolic process 174 15
GO:BP cellular process 17828 410
GO:BP phosphorus metabolic process 2832 94
GO:BP response to external stimulus 2912 96
GO:BP hexose metabolic process 247 18
GO:BP long-chain fatty acid metabolic process 115 12
GO:BP response to drug 459 26
GO:BP response to stress 3817 118
GO:BP regulation of small molecule metabolic process 355 22
GO:BP nucleotide metabolic process 466 26
GO:BP ribose phosphate metabolic process 385 23
GO:BP homeostatic process 1922 69
GO:BP aspartate family amino acid catabolic process 15 5
GO:BP cellular carbohydrate metabolic process 310 20
GO:BP detoxification 123 12
GO:BP transmembrane transport 1533 58
GO:BP regulation of endopeptidase activity 451 25
GO:BP cellular response to hormone stimulus 600 30
GO:BP lysosomal protein catabolic process 16 5
GO:BP aromatic amino acid family catabolic process 16 5
GO:BP cell death 2136 74
GO:BP response to toxic substance 240 17
GO:BP gland development 513 27
GO:BP cellular response to xenobiotic stimulus 106 11
GO:BP regulation of inflammatory response 347 21
GO:BP primary alcohol metabolic process 90 10
GO:BP response to steroid hormone 352 21
GO:BP wound healing 380 22
GO:BP regulation of cell population proliferation 1753 63
GO:BP regulation of glucose metabolic process 133 12
GO:BP cellular response to endogenous stimulus 1333 51
GO:BP hepatocyte proliferation 30 6
GO:BP epithelial cell proliferation involved in liver morphogenesis 30 6
GO:BP response to xenobiotic stimulus 115 11
GO:BP L-ascorbic acid biosynthetic process 4 3
GO:BP macromolecule localization 2897 92
GO:BP nucleoside phosphate biosynthetic process 232 16
GO:BP mammary gland epithelial cell proliferation 31 6
GO:BP glutamate metabolic process 31 6
GO:BP carbohydrate biosynthetic process 209 15
GO:BP secondary alcohol metabolic process 141 12
GO:BP organic cyclic compound catabolic process 458 24
GO:BP glucose metabolic process 212 15
GO:BP nicotinamide nucleotide biosynthetic process 20 5
GO:BP pyridine nucleotide biosynthetic process 20 5
GO:BP organic anion transport 372 21
GO:BP nitrogen compound transport 1986 68
GO:BP cellular lipid catabolic process 214 15
GO:BP monocarboxylic acid catabolic process 122 11
GO:BP nitric oxide metabolic process 82 9
GO:BP response to nutrient levels 523 26
GO:BP regulation of cellular carbohydrate metabolic process 167 13
GO:BP ribonucleotide metabolic process 376 21
GO:BP gland morphogenesis 144 12
GO:BP xenobiotic metabolic process 102 10
GO:BP response to lipid 980 40
GO:BP cellular response to nutrient levels 217 15
GO:BP negative regulation of proteolysis 379 21
GO:BP olefinic compound metabolic process 124 11
GO:BP response to extracellular stimulus 559 27
GO:BP regulation of cell death 1740 61
GO:BP reactive nitrogen species metabolic process 84 9
GO:BP response to peptide 531 26
GO:BP glycerolipid metabolic process 384 21
GO:BP pigment metabolic process 68 8
GO:BP ion transport 1572 56
GO:BP cholesterol metabolic process 129 11
GO:BP negative regulation of endopeptidase activity 278 17
GO:BP cellular response to extracellular stimulus 252 16
GO:BP lipid storage 88 9
GO:BP pyridine-containing compound biosynthetic process 23 5
GO:BP regulation of protein exit from endoplasmic reticulum 23 5
GO:BP regulation of response to stress 1254 47
GO:BP negative regulation of biological process 5544 153
GO:BP response to peptide hormone 452 23
GO:BP arachidonic acid metabolic process 70 8
GO:BP nitrogen compound metabolic process 9669 244
GO:BP regulation of multicellular organismal process 2788 87
GO:BP hexose biosynthetic process 90 9
GO:BP regulation of developmental process 2591 82
GO:BP retinoid metabolic process 71 8
GO:BP animal organ regeneration 91 9
GO:BP regulation of proteolysis 778 33
GO:BP icosanoid metabolic process 134 11
GO:BP positive regulation of inflammatory response 134 11
GO:BP positive regulation of lipid biosynthetic process 91 9
GO:BP regeneration 232 15
GO:BP lipid localization 459 23
GO:BP programmed cell death 1975 66
GO:BP negative regulation of peptidase activity 287 17
GO:BP biosynthetic process 5882 160
GO:BP aromatic compound catabolic process 432 22
GO:BP glomerular filtration 25 5
GO:BP fatty acid oxidation 114 10
GO:BP triglyceride biosynthetic process 39 6
GO:BP negative regulation of cellular process 5068 141
GO:BP sterol metabolic process 137 11
GO:BP complement activation, alternative pathway 14 4
GO:BP positive regulation of response to wounding 74 8
GO:BP pyruvate biosynthetic process 6 3
GO:BP chemical homeostasis 1245 46
GO:BP cell population proliferation 2072 68
GO:BP response to nutrient 187 13
GO:BP renal filtration 26 5
GO:BP cellular response to external stimulus 322 18
GO:BP regulation of response to wounding 165 12
GO:BP regulation of programmed cell death 1587 55
GO:BP diterpenoid metabolic process 77 8
GO:BP nitric oxide biosynthetic process 77 8
GO:BP regulation of response to external stimulus 904 36
GO:BP lipid homeostasis 167 12
GO:BP lipid oxidation 120 10
GO:BP protein exit from endoplasmic reticulum 42 6
GO:BP purine ribonucleotide metabolic process 358 19
GO:BP negative regulation of cell death 1119 42
GO:BP response to metal ion 388 20
GO:BP fatty acid catabolic process 99 9
GO:BP cellular response to organonitrogen compound 643 28
GO:BP cellular response to nitrogen compound 710 30
GO:BP secondary metabolic process 61 7
GO:BP negative regulation of protein metabolic process 1128 42
GO:BP positive regulation of steroid hormone biosynthetic process 7 3
GO:BP L-ascorbic acid metabolic process 7 3
GO:BP regulation of body fluid levels 364 19
GO:BP nicotinamide nucleotide metabolic process 29 5
GO:BP pyridine nucleotide metabolic process 29 5
GO:BP negative regulation of hydrolase activity 457 22
GO:BP regulation of carbohydrate metabolic process 199 13
GO:BP cellular response to oxygen-containing compound 1247 45
GO:BP regulation of wound healing 126 10
GO:BP hormone biosynthetic process 63 7
GO:BP positive regulation of hydrolase activity 653 28
GO:BP negative regulation of cellular protein metabolic process 1068 40
GO:BP glutamine family amino acid biosynthetic process 17 4
GO:BP fatty acid biosynthetic process 151 11
GO:BP response to glucocorticoid 176 12
GO:BP nucleotide biosynthetic process 229 14
GO:BP anion transport 529 24
GO:BP terpenoid metabolic process 85 8
GO:BP sarcosine metabolic process 2 2
GO:BP regulation of transcription from RNA polymerase II promoter in response to iron 2 2
GO:BP retinol metabolic process 47 6
GO:BP response to gonadotropin 31 5
GO:BP purine-containing compound metabolic process 406 20
GO:BP xenobiotic detoxification by transmembrane export across the plasma membrane 8 3
GO:BP erythrose 4-phosphate/phosphoenolpyruvate family amino acid catabolic process 8 3
GO:BP regulation of phagocytosis 108 9
GO:BP glycosyl compound metabolic process 86 8
GO:BP ketone catabolic process 18 4
GO:BP malate metabolic process 8 3
GO:BP L-phenylalanine catabolic process 8 3
GO:BP inflammatory response 732 30
GO:BP neutral lipid biosynthetic process 48 6
GO:BP acylglycerol biosynthetic process 48 6
GO:BP carbohydrate derivative catabolic process 156 11
GO:BP response to chemical 5544 149
GO:BP gluconeogenesis 87 8
GO:BP response to inorganic substance 604 26
GO:BP positive regulation of response to stimulus 2198 69
GO:BP pyridine-containing compound metabolic process 33 5
GO:BP endoplasmic reticulum tubular network organization 19 4
GO:BP enzyme linked receptor protein signaling pathway 916 35
GO:BP regulation of mammary gland epithelial cell proliferation 19 4
GO:BP sulfur amino acid metabolic process 33 5
GO:BP response to copper ion 33 5
GO:BP regulation of defense response 575 25
GO:BP purine nucleotide metabolic process 385 19
GO:BP steroid biosynthetic process 161 11
GO:BP regulation of cysteine-type endopeptidase activity involved in apoptotic process 214 13
GO:BP regulation of apoptotic process 1550 52
GO:BP vitamin metabolic process 70 7
GO:BP bile acid and bile salt transport 34 5
GO:BP negative regulation of cell population proliferation 715 29
GO:BP epithelial fluid transport 9 3
GO:BP regulation of epithelial cell proliferation 359 18
GO:BP erythrose 4-phosphate/phosphoenolpyruvate family amino acid metabolic process 9 3
GO:BP development of secondary female sexual characteristics 9 3
GO:BP L-phenylalanine metabolic process 9 3
GO:BP pyruvate metabolic process 114 9
GO:BP cellular response to copper ion 20 4
GO:BP response to stilbenoid 20 4
GO:BP glutamine family amino acid metabolic process 71 7
GO:BP regulation of triglyceride metabolic process 52 6
GO:BP epithelial cell proliferation 424 20
GO:BP protein-containing complex subunit organization 1636 54
GO:BP intracellular transport 1409 48
GO:BP transmembrane receptor protein tyrosine kinase signaling pathway 587 25
GO:BP regulation of ERBB signaling pathway 73 7
GO:BP quinone metabolic process 36 5
GO:BP positive regulation of ERBB signaling pathway 36 5
GO:BP apoptotic process 1919 61
GO:BP response to corticosteroid 194 12
GO:BP protein homotetramerization 54 6
GO:BP water-soluble vitamin biosynthetic process 10 3
GO:BP protein-containing complex assembly 1462 49
GO:BP negative regulation of cell maturation 10 3
GO:BP cellular response to peptide 370 18
GO:BP positive regulation of sister chromatid cohesion 10 3
GO:BP porphyrin-containing compound metabolic process 37 5
GO:BP mammary gland development 170 11
GO:BP serine family amino acid metabolic process 37 5
GO:BP regulation of lipid storage 55 6
GO:BP positive regulation of wound healing 55 6
GO:BP vitamin biosynthetic process 22 4
GO:BP regulation of fatty acid beta-oxidation 22 4
GO:BP regulation of hepatocyte proliferation 22 4
GO:BP positive regulation of biological process 6305 164
GO:BP positive regulation of phagocytosis 76 7
GO:BP NADP metabolic process 38 5
GO:BP organic substance biosynthetic process 5779 152
GO:BP positive regulation of defense response 256 14
GO:BP temperature homeostasis 173 11
GO:BP regulation of fatty acid metabolic process 99 8
GO:BP positive regulation of lipid storage 23 4
GO:BP aspartate family amino acid biosynthetic process 23 4
GO:BP macrophage migration 57 6
GO:BP chylomicron remodeling 3 2
GO:BP fumarate metabolic process 3 2
GO:BP ribose phosphate biosynthetic process 175 11
GO:BP isoleucine biosynthetic process 3 2
GO:BP low-density lipoprotein particle mediated signaling 3 2
GO:BP ammonia assimilation cycle 3 2
GO:BP lipoprotein particle mediated signaling 3 2
GO:BP cellular nitrogen compound catabolic process 411 19
GO:BP regulation of immune system process 1406 47
GO:BP system development 4876 131
GO:BP kynurenine metabolic process 11 3
GO:BP regulation of response to stimulus 3851 107
GO:BP xenobiotic transport 40 5
GO:BP regulation of renal system process 40 5
GO:BP response to oxidative stress 447 20
GO:BP regulation of platelet-derived growth factor receptor signaling pathway 24 4
GO:BP glutamine metabolic process 24 4
GO:BP negative regulation of programmed cell death 1002 36
GO:BP regulation of protein-containing complex assembly 448 20
GO:BP positive regulation of transport 1005 36
GO:BP regulation of cell differentiation 1649 53
GO:BP protein transport 1535 50
GO:BP cellular response to drug 81 7
GO:BP regulation of cysteine-type endopeptidase activity 237 13
GO:BP CDP-diacylglycerol biosynthetic process 12 3
GO:BP development of secondary sexual characteristics 12 3
GO:BP organic acid transport 327 16
GO:BP carboxylic acid transport 297 15
GO:BP response to estradiol 155 10
GO:BP regulation of glomerular filtration 12 3
GO:BP protein tetramerization 82 7
GO:BP positive regulation of hormone biosynthetic process 12 3
GO:BP response to cadmium ion 61 6
GO:BP regulation of localization 2868 83
GO:BP C21-steroid hormone metabolic process 42 5
GO:BP one-carbon metabolic process 42 5
GO:BP isoprenoid metabolic process 107 8
GO:BP renal system process involved in regulation of systemic arterial blood pressure 26 4
GO:BP iron ion transport 63 6
GO:BP regulation of lipid biosynthetic process 187 11
GO:BP fructose metabolic process 13 3
GO:BP dicarboxylic acid biosynthetic process 13 3
GO:BP response to folic acid 13 3
GO:BP alditol phosphate metabolic process 13 3
GO:BP CDP-diacylglycerol metabolic process 13 3
GO:BP positive regulation of nuclear-transcribed mRNA poly(A) tail shortening 13 3
GO:BP positive regulation of protein exit from endoplasmic reticulum 13 3
GO:BP formation of translation preinitiation complex 13 3
GO:BP regulation of gluconeogenesis 64 6
GO:BP regulation of blood coagulation 64 6
GO:BP positive regulation of small molecule metabolic process 161 10
GO:BP thyroid hormone metabolic process 27 4
GO:BP cellular homeostasis 956 34
GO:BP regulation of cell maturation 27 4
GO:BP estrogen metabolic process 27 4
GO:BP lipid modification 218 12
GO:BP response to 2,3,7,8-tetrachlorodibenzodioxine 4 2
GO:BP NADP biosynthetic process 4 2
GO:BP porphyrin-containing compound catabolic process 4 2
GO:BP heme catabolic process 4 2
GO:BP multicellular organism development 5441 142
GO:BP negative regulation of dendritic cell differentiation 4 2
GO:BP endoplasmic reticulum tubular network membrane organization 4 2
GO:BP L-kynurenine catabolic process 4 2
GO:BP endoplasmic reticulum tubular network formation 4 2
GO:BP pigment catabolic process 4 2
GO:BP cellular response to peptide hormone stimulus 309 15
GO:BP response to decreased oxygen levels 341 16
GO:BP regulation of hemostasis 66 6
GO:BP neuron death 406 18
GO:BP positive regulation of fatty acid metabolic process 46 5
GO:BP tetrapyrrole metabolic process 46 5
GO:BP renal system process 113 8
GO:BP carbohydrate derivative biosynthetic process 574 23
GO:BP energy reserve metabolic process 89 7
GO:BP growth hormone receptor signaling pathway 14 3
GO:BP anatomical structure development 5987 154
GO:BP regulation of nuclear-transcribed mRNA poly(A) tail shortening 14 3
GO:BP aldehyde catabolic process 14 3
GO:BP copper ion transport 14 3
GO:BP regulation of coagulation 67 6
GO:BP regulation of nitric oxide biosynthetic process 67 6
GO:BP positive regulation of cell population proliferation 1045 36
GO:BP sphingolipid metabolic process 140 9
GO:BP heterocycle catabolic process 410 18
GO:BP regulation of erythrocyte differentiation 47 5
GO:BP response to lipoprotein particle 29 4
GO:BP regulation of epidermal growth factor receptor signaling pathway 68 6
GO:BP defense response 1705 53
GO:BP regulation of nitric oxide metabolic process 69 6
GO:CC cytoplasm 11093 340
GO:CC organelle membrane 3076 143
GO:CC endoplasmic reticulum 1761 88
GO:CC endomembrane system 4006 152
GO:CC endoplasmic reticulum membrane 993 61
GO:CC endoplasmic reticulum subcompartment 999 61
GO:CC nuclear outer membrane-endoplasmic reticulum membrane network 1018 61
GO:CC intracellular anatomical structure 14111 372
GO:CC organelle subcompartment 1580 80
GO:CC mitochondrion 1827 82
GO:CC envelope 1176 61
GO:CC organelle envelope 1176 61
GO:CC mitochondrial membrane 677 43
GO:CC mitochondrial envelope 736 44
GO:CC intracellular membrane-bounded organelle 11363 307
GO:CC membrane-bounded organelle 11812 312
GO:CC mitochondrial inner membrane 451 30
GO:CC cellular anatomical entity 19567 445
GO:CC apical plasma membrane 388 26
GO:CC intracellular organelle 12510 320
GO:CC apical part of cell 474 29
GO:CC organelle inner membrane 510 30
GO:CC organelle 12827 324
GO:CC membrane 10122 266
GO:CC cytosol 3849 118
GO:CC lytic vacuole 468 25
GO:CC lysosome 468 25
GO:CC bounding membrane of organelle 1676 61
GO:CC vacuole 562 28
GO:CC basal part of cell 291 18
GO:CC endosome membrane 403 22
GO:CC peroxisome 148 12
GO:CC microbody 148 12
GO:CC basal plasma membrane 272 17
GO:CC plasma membrane region 1318 49
GO:CC vesicle 2077 69
GO:CC Golgi apparatus 1449 52
GO:CC vesicle membrane 833 34
GO:CC cytoplasmic vesicle 1931 64
GO:CC intracellular vesicle 1937 64
GO:CC vacuolar membrane 280 16
GO:CC endosome 870 34
GO:CC brush border 134 10
GO:CC basolateral plasma membrane 239 14
GO:CC lytic vacuole membrane 219 13
GO:CC lysosomal membrane 219 13
GO:CC brush border membrane 73 7
GO:CC Golgi apparatus subcompartment 746 29
GO:CC azurophil granule 12 3
GO:CC primary lysosome 12 3
GO:CC microvillus 106 8
GO:CC membrane raft 392 18
GO:CC membrane microdomain 393 18
GO:MF catalytic activity 5665 223
GO:MF oxidoreductase activity 815 63
GO:MF oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen 217 22
GO:MF monooxygenase activity 159 18
GO:MF small molecule binding 2543 95
GO:MF anion binding 2420 91
GO:MF vitamin binding 141 16
GO:MF identical protein binding 2140 82
GO:MF oxidoreductase activity, acting on CH-OH group of donors 154 16
GO:MF iron ion binding 211 18
GO:MF lyase activity 198 17
GO:MF heme binding 183 16
GO:MF pyridoxal phosphate binding 54 9
GO:MF vitamin B6 binding 55 9
GO:MF oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor 143 14
GO:MF tetrapyrrole binding 192 16
GO:MF ion binding 5862 168
GO:MF transaminase activity 22 6
GO:MF glutathione transferase activity 33 7
GO:MF transferase activity, transferring nitrogenous groups 23 6
GO:MF hydrolase activity 2353 79
GO:MF acyltransferase activity, transferring groups other than amino-acyl groups 232 16
GO:MF transferase activity 2277 76
GO:MF acyltransferase activity 263 17
GO:MF active transmembrane transporter activity 346 20
GO:MF nucleoside phosphate binding 2185 73
GO:MF nucleotide binding 2185 73
GO:MF transferase activity, transferring alkyl or aryl (other than methyl) groups 65 8
GO:MF transition metal ion binding 1064 42
GO:MF nickel cation binding 5 3
GO:MF aromatase activity 36 6
GO:MF steroid hydroxylase activity 69 8
GO:MF bile acid binding 13 4
GO:MF monocarboxylic acid transmembrane transporter activity 56 7
GO:MF transporter activity 1137 43
GO:MF magnesium ion binding 218 14
GO:MF lipid transporter activity 147 11
GO:MF 1-acyl-2-lysophosphatidylserine acylhydrolase activity 7 3
GO:MF phosphatidylserine 1-acylhydrolase activity 7 3
GO:MF carboxylic acid binding 174 12
GO:MF lipid binding 786 32
GO:MF amide binding 367 19
GO:MF N-acyltransferase activity 103 9
GO:MF protein-containing complex binding 1464 51
GO:MF carboxylic ester hydrolase activity 153 11
GO:MF oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen 65 7
GO:MF L-threonine ammonia-lyase activity 2 2
GO:MF hormone binding 85 8
GO:MF organic hydroxy compound transmembrane transporter activity 47 6
GO:MF carboxylic acid transmembrane transporter activity 155 11
GO:MF organic acid transmembrane transporter activity 156 11
GO:MF flavin adenine dinucleotide binding 90 8
GO:MF steroid binding 114 9
GO:MF phospholipase A1 activity 9 3
GO:MF peptide hormone binding 51 6
GO:MF oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen 54 6
GO:MF organic anion transmembrane transporter activity 172 11
GO:MF triglyceride binding 3 2
GO:MF peptidase regulator activity 255 14
GO:MF long-chain fatty acid omega-hydroxylase activity 3 2
GO:MF sphingolipid delta-4 desaturase activity 3 2
GO:MF lipase activity 124 9
GO:MF pattern recognition receptor activity 23 4
GO:MF estrogen 2-hydroxylase activity 3 2
GO:MF purine nucleobase binding 3 2
GO:MF L-serine ammonia-lyase activity 3 2
GO:MF bile acid transmembrane transporter activity 23 4
GO:MF protein binding 10189 248
GO:MF oxidoreductase activity, acting on paired donors, with oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water 11 3
GO:MF ATPase-coupled transmembrane transporter activity 125 9
GO:MF monocarboxylic acid binding 80 7
GO:MF primary active transmembrane transporter activity 128 9
GO:MF carbon-sulfur lyase activity 12 3
GO:MF triglyceride lipase activity 42 5
GO:MF peptidase inhibitor activity 214 12
GO:MF hydrolase activity, acting on ester bonds 735 28
GO:MF acylglycerol lipase activity 13 3
GO:MF carbon-nitrogen lyase activity 13 3
GO:MF oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen 27 4
GO:MF alcohol dehydrogenase (NADP+) activity 27 4
GO:MF serine-type peptidase activity 217 12
GO:MF sn-1-glycerol-3-phosphate C16:0-DCA-CoA acyl transferase activity 4 2
GO:MF ferrous iron transmembrane transporter activity 4 2
GO:MF N-acetyl-beta-D-galactosaminidase activity 4 2
GO:MF thrombospondin receptor activity 4 2
GO:MF glycerol-3-phosphate O-acyltransferase activity 4 2
GO:MF oxidoreductase activity, acting on single donors with incorporation of molecular oxygen 28 4
GO:MF folic acid binding 14 3
GO:MF serine hydrolase activity 222 12
GO:MF retinol binding 14 3
GO:MF steroid dehydrogenase activity 48 5
GO:MF aldo-keto reductase (NADP) activity 30 4
GO:MF transmembrane transporter activity 1053 36
GO:MF oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen 15 3
GO:MF xenobiotic transmembrane transporter activity 30 4
GO:MF estrogen receptor binding 49 5
GO:MF peptide binding 290 14
GO:MF organic acid binding 145 9
HP Abnormal circulating metabolite concentration 1099 64
HP Abnormal circulating carboxylic acid concentration 216 23
HP Autosomal recessive inheritance 2708 114
HP Abnormality of metabolism/homeostasis 2240 96
HP Abnormal circulating amino acid concentration 121 14
HP Abnormal urine metabolite level 428 29
KEGG Metabolic pathways 1563 110
KEGG Chemical carcinogenesis 101 15
KEGG Bile secretion 100 15
KEGG Biosynthesis of amino acids 78 12
KEGG Cysteine and methionine metabolism 52 9
KEGG Glutathione metabolism 71 10
KEGG Drug metabolism - cytochrome P450 71 10
KEGG Metabolism of xenobiotics by cytochrome P450 73 10
KEGG Carbon metabolism 121 13
KEGG Cholesterol metabolism 49 8
KEGG Glycine, serine and threonine metabolism 39 7
KEGG Lysosome 131 13
KEGG Pyruvate metabolism 44 7
KEGG Complement and coagulation cascades 92 10
KEGG Glycerophospholipid metabolism 98 10
KEGG Alanine, aspartate and glutamate metabolism 38 6
KEGG Mineral absorption 53 7
KEGG Tyrosine metabolism 39 6
KEGG Steroid hormone biosynthesis 91 9
KEGG Drug metabolism - other enzymes 92 9
KEGG Glyoxylate and dicarboxylate metabolism 31 5
KEGG Arginine biosynthesis 20 4
KEGG Retinol metabolism 97 9
KEGG Phenylalanine metabolism 22 4
REAC Metabolism 1679 118
REAC Metabolism of amino acids and derivatives 234 29
REAC Metabolism of lipids 573 40
REAC Biological oxidations 204 19
REAC Phenylalanine and tyrosine metabolism 10 4
REAC Bile acid and bile salt metabolism 40 7
REAC Methylation 12 4
REAC Recycling of bile acids and salts 14 4
REAC Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol 24 5
REAC Transport of small molecules 635 35
REAC Metabolism of steroids 112 11
REAC Heme degradation 14 4
REAC Glutamate and glutamine metabolism 13 4
REAC Pyruvate metabolism and Citric Acid (TCA) cycle 50 7
TF Factor: GKLF; motif: NNNRGGNGNGGSN 15302 377
TF Factor: Mxi1; motif: NCACGTGGSNGNNNN 3073 104
TF Factor: GKLF; motif: NNNRGGNGNGGSN; match class: 1 10998 286
TF Factor: Egr-2; motif: GCGTGGGCGG 7210 203
TF Factor: BCL6B; motif: NNNNCCGCCCCWNNNN 13664 337
TF Factor: GKLF; motif: NNRRGRRNGNSNNN 12950 322
TF Factor: ZFP187; motif: NNGMCCTNGTCCNYNN 2555 87
TF Factor: ZBP89; motif: CCCCKCCCCCNN; match class: 1 3885 121
TF Factor: Pax-4; motif: NNNNNYCACCCB 18716 428
TF Factor: Kid3; motif: CCACN; match class: 1 21165 462
TF Factor: Arnt; motif: NNNNNRTCACGTGAYNNNNN; match class: 1 7087 195
TF Factor: Arnt; motif: NNNNNRTCACGTGAYNNNNN 7087 195
TF Factor: ZF5; motif: NRNGNGCGCGCWN 14469 350
TF Factor: Sp1; motif: GGNGGGGGNGGGGGMGGGGCNGGG 10752 274
TF Factor: ZBP89; motif: CCCCKCCCCCNN 8105 217
TF Factor: Hes1; motif: NNCACGYGNN; match class: 1 11386 287
TF Factor: FOXN4; motif: NNWANNCGWMCGCGTCNNNNMT 16009 378
TF Factor: E2F-1; motif: GNGGGCGGGRMN 14228 344
TF Factor: FOXN4; motif: NNWANNCGWMCGCGTCNNNNMT; match class: 1 12768 315
TF Factor: c-Myc:Max; motif: NNACCACGTGGTNN; match class: 1 7970 213
TF Factor: c-Myc:Max; motif: NNACCACGTGGTNN 7970 213
TF Factor: PPARgamma:RXR-alpha; motif: NTRGGNCARAGGKCA; match class: 1 5253 151
TF Factor: c-Myc:Max; motif: NNNNNNNCACGTGNNNNNNN; match class: 1 7236 196
TF Factor: c-Myc:Max; motif: NNNNNNNCACGTGNNNNNNN 7236 196
TF Factor: WT1; motif: NNGGGNGGGSGN 7486 201
TF Factor: WT1; motif: SMCNCCNSC 8128 215
TF Factor: E2F-3; motif: GGCGGGN 11268 282
TF Factor: PPAR,; motif: RGGNCAAAGGTCA 2376 79
TF Factor: SP1:SP3; motif: CCSCCCCCYCC 6684 182
TF Factor: USF2; motif: CASGYG 6304 173
TF Factor: USF2; motif: CASGYG; match class: 1 6304 173
TF Factor: MAZ; motif: NKGGGAGGGGRGGR 7957 210
TF Factor: ZF5; motif: GSGCGCGR 14821 353
TF Factor: Klf15; motif: RGGGMGGRGNNGGGGGNGG 3269 101
TF Factor: HIF-1alpha; motif: NCACGT 6382 174
TF Factor: NF-E2; motif: CATGACTCAGCANNCN; match class: 1 47 7
TF Factor: CKROX; motif: SCCCTCCCC 6334 173
TF Factor: E2F-4; motif: NTTTCSCGCC 10545 265
TF Factor: ARNTLIKE; motif: NNNSCACGTG 5261 148
TF Factor: MAZ; motif: GGGGAGGG 8416 219
TF Factor: C-Myc; motif: NGCCACGTGNN 6226 170
TF Factor: E2F-4; motif: NTTTCSCGCC; match class: 1 5364 150
TF Factor: ZF5; motif: GYCGCGCARNGCNN 9484 241
TF Factor: CACD; motif: CCACRCCC 10859 270
TF Factor: BEN; motif: CAGCGRNV 16234 378
TF Factor: Zfp281; motif: NNCCCCCCCCCCMYC 3971 116
TF Factor: E2F-4; motif: GCGGGAAANA 10318 258
TF Factor: GKLF; motif: NNRRGRRNGNSNNN; match class: 1 8470 218
TF Factor: USF; motif: GYCACGTGNC 3536 105
TF Factor: Sp1; motif: NNGGGGCGGGGNN 8939 228
TF Factor: c-Myc; motif: KACCACGTGSYY 5491 151
TF Factor: SP1:SP3; motif: CCSCCCCCYCC; match class: 1 3378 101
TF Factor: Osx; motif: CCNCCCCCNNN 6158 166
TF Factor: ZF5; motif: GYCGCGCARNGCNN; match class: 1 5819 158
TF Factor: HNF4; motif: TGAMCTTTGNCCN 2230 72
TF Factor: Pax-4; motif: NNNNNYCACCCB; match class: 1 14458 342
TF Factor: NGFI-C; motif: WTGCGTGGGYGG 5000 139
TF Factor: VDR; motif: GGGKNARNRRGGWSA 10051 251
TF Factor: E2F-4; motif: NGGGGGCGGGRMNN 6987 184
TF Factor: MAZ; motif: NKGGGAGGGGRGGR; match class: 1 4159 119
TF Factor: E2F; motif: GGCGSG 10391 258
TF Factor: Hes1; motif: NNCACGYGNN 15504 362
TF Factor: BTEB2; motif: GNAGGGGGNGGGSSNN 4977 138
TF Factor: TEL1; motif: CNCGGAANNN 10420 258
TF Factor: HNF4alpha1; motif: NRGGNCAAAGGTCAN 2111 68
TF Factor: Pax-5; motif: BCNNNRNGCANBGNTGNRTAGCSGCHNB; match class: 1 3991 114
TF Factor: Tcfl5; motif: NNCNCGNGNN; match class: 1 6337 168
TF Factor: STAT1; motif: NNNSANTTCCGGGAANTGNSN; match class: 1 2881 87
TF Factor: Tcfl5; motif: NNCNCGNGNN 6337 168
TF Factor: VDR; motif: GGGKNARNRRGGWSA; match class: 1 3798 109
TF Factor: Clock; motif: CNGNCACGTGNNNM 1665 56
TF Factor: Sp1; motif: GGGGCGGGGC 8654 219
TF Factor: E2F-4; motif: GNNGGCGGGAAN 5907 158
TF Factor: Myc; motif: CACGTGS 5129 140
TF Factor: Sp1; motif: GGNGGGGGNGGGGGMGGGGCNGGG; match class: 1 7397 191
TF Factor: Sp5; motif: RNGGRGGNGGRGNNGGGGGAGGRG; match class: 1 1948 63
TF Factor: CREB,; motif: NTGACGTNA 8122 207
TF Factor: AP-2beta; motif: GCNNNGGSCNGVGGGN 5101 139
TF Factor: LKLF; motif: CNCCACCCS 5803 155
TF Factor: ZF5; motif: GSGCGCGR; match class: 1 12032 290
TF Factor: AhR,; motif: NRCGTGNGN 4421 123
TF Factor: Sp1; motif: NGGGGGCGGGGYN 8784 221
TF Factor: NF-E2; motif: CATGACTCAGCANNCN 1201 43
TF Factor: Max; motif: NMSCACGTGGC 1243 44
TF Factor: Sp1; motif: NGGGGCGGGGN 9122 228
TF Factor: Max; motif: NNANCACGTGNTNN 7339 189
TF Factor: Max; motif: NNANCACGTGNTNN; match class: 1 7339 189
TF Factor: Sp1; motif: GGGGCGGGGT 8345 211
TF Factor: CPBP; motif: SNCCCNN; match class: 1 19929 441
TF Factor: CP2/LBP-1c/LSF; motif: GCTGGNTNGNNCYNG; match class: 1 2369 73
TF Factor: N-Myc; motif: NNCCACGTGNNN 4316 120
TF Factor: LKLF; motif: GGGGTGGKSN 9186 229
TF Factor: SP4; motif: NNWAGGCGTGNCNNN 4923 134
TF Factor: E2F-1; motif: GNGGGCGGGRMN; match class: 1 10601 259
TF Factor: WT1; motif: NNGGGNGGGSGN; match class: 1 3877 109
TF Factor: CTCF; motif: NAGGGGGCGCNNKNNNN 14310 335
TF Factor: bach2; motif: TGCTGAGTCAY; match class: 1 21 4
TF Factor: AP-2alphaA; motif: ANNGCCTNAGGSNNT 5089 137
TF Factor: MYB; motif: NNAACTGN 1535 51
TF Factor: C-Myc; motif: NGCCACGTGNN; match class: 1 4317 119
TF Factor: Smad3; motif: NNCTSNCWSCWS 10078 247
TF Factor: Sp5; motif: RNGGRGGNGGRGNNGGGGGAGGRG 4848 131
TF Factor: SREBP-1; motif: CACSCCA; match class: 1 2459 74
TF Factor: Tax/CREB; motif: GGGGGTTGACGYANA 5338 142
TF Factor: WT1; motif: NGCGGGGGGGTSMMCYN 5297 141
TF Factor: Zic3; motif: NMCCCCCGGGGGGGN; match class: 1 2035 63
TF Factor: STAT3; motif: NNTCAYTTCCYGKNA; match class: 1 1373 46
TF Factor: SP2; motif: GNNGGGGGCGGGGSN 7094 181
TF Factor: PPAR; motif: TGACCTTTGNCCY 6027 157
TF Factor: SREBP-2; motif: NNGYCACNNSMN 7690 194
TF Factor: E2F; motif: GGCGSG; match class: 1 7016 179
TF Factor: c-Myc:Max; motif: GCCAYGYGSN 7338 186
TF Factor: c-Myc:Max; motif: GCCAYGYGSN; match class: 1 2409 72
TF Factor: Mycn; motif: NSCACGTGGC 154 10
TF Factor: GKLF; motif: GCCMCRCCCNNN 7840 197
WP Metapathway biotransformation 141 16
WP One carbon metabolism and related pathways 52 8
WP Oxidation by Cytochrome P450 40 7
WP Amino Acid metabolism 95 11
WP Retinol metabolism 39 7

2.2.6 Functional Enrichment - Liver TCDD-AhR Regulated

kable(Liver_Interx_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size), 
      table.attr = "class=\"striped\"", format = "html")
source term_name term_size intersection_size
CORUM Parvulin-associated pre-rRNP complex 46 9
GO:BP cellular amide metabolic process 1077 55
GO:BP cellular metabolic process 10350 214
GO:BP small molecule metabolic process 1713 69
GO:BP organonitrogen compound biosynthetic process 1570 65
GO:BP organic acid metabolic process 944 49
GO:BP metabolic process 11429 226
GO:BP peptide metabolic process 835 45
GO:BP carboxylic acid metabolic process 896 46
GO:BP oxoacid metabolic process 908 46
GO:BP obsolete oxidation-reduction process 548 35
GO:BP organic substance metabolic process 10989 214
GO:BP peptide biosynthetic process 677 37
GO:BP monocarboxylic acid metabolic process 616 35
GO:BP amide biosynthetic process 793 40
GO:BP translation 657 36
GO:BP organic acid biosynthetic process 290 24
GO:BP catabolic process 2399 75
GO:BP primary metabolic process 10243 200
GO:BP organonitrogen compound metabolic process 6326 142
GO:BP carboxylic acid biosynthetic process 282 22
GO:BP cellular lipid metabolic process 994 42
GO:BP organic substance catabolic process 1985 64
GO:BP small molecule biosynthetic process 617 32
GO:BP cellular catabolic process 2059 65
GO:BP lipid metabolic process 1344 48
GO:BP sulfur compound metabolic process 317 21
GO:BP fatty acid metabolic process 425 24
GO:BP regulation of biological quality 3876 94
GO:BP ribonucleoprotein complex biogenesis 413 23
GO:BP biosynthetic process 5882 125
GO:BP cytoplasmic translation 101 11
GO:BP ribosome assembly 63 9
GO:BP organic substance biosynthetic process 5779 121
GO:BP small molecule catabolic process 346 19
GO:BP monocarboxylic acid biosynthetic process 194 14
GO:BP ribosome biogenesis 288 17
GO:BP nitrogen compound metabolic process 9669 176
GO:BP ribonucleoprotein complex assembly 182 13
GO:BP cellular biosynthetic process 5715 117
GO:BP ribonucleoprotein complex subunit organization 188 13
GO:BP toxin metabolic process 17 5
GO:BP benzene-containing compound metabolic process 30 6
GO:BP glutathione metabolic process 70 8
GO:BP response to toxic substance 240 14
GO:BP cellular modified amino acid metabolic process 179 12
GO:BP organophosphate metabolic process 891 30
GO:BP fatty acid biosynthetic process 151 11
GO:BP gland development 513 21
GO:BP NADP metabolic process 38 6
GO:BP unsaturated fatty acid metabolic process 133 10
GO:BP glycosyl compound metabolic process 86 8
GO:BP liver development 173 11
GO:BP response to xenobiotic stimulus 115 9
GO:BP response to hormone 912 29
GO:BP rRNA processing 208 12
GO:BP protein metabolic process 5474 108
GO:BP hepaticobiliary system development 176 11
GO:BP xenobiotic catabolic process 15 4
GO:BP cell redox homeostasis 29 5
GO:BP ribosomal small subunit biogenesis 69 7
GO:BP cellular lipid catabolic process 214 12
GO:BP mature ribosome assembly 6 3
GO:BP rRNA metabolic process 217 12
GO:BP carboxylic acid catabolic process 221 12
GO:BP organonitrogen compound catabolic process 1249 35
GO:BP xenobiotic metabolic process 102 8
GO:BP cellular protein metabolic process 4815 96
GO:BP cellular response to chemical stimulus 3097 68
GO:BP monoacylglycerol catabolic process 7 3
GO:BP very long-chain fatty acid metabolic process 33 5
GO:BP carbohydrate metabolic process 587 21
GO:BP ketone catabolic process 18 4
GO:BP organic acid catabolic process 228 12
GO:BP nucleobase metabolic process 34 5
GO:BP positive regulation of cellular amide metabolic process 163 10
GO:BP regulation of angiogenesis 305 14
GO:BP purine nucleobase metabolic process 19 4
GO:BP cellular response to xenobiotic stimulus 106 8
GO:BP positive regulation of translation 135 9
GO:BP cellular nitrogen compound metabolic process 6201 117
GO:BP carbohydrate derivative metabolic process 975 29
GO:BP lipid biosynthetic process 647 22
GO:BP blood vessel morphogenesis 647 22
GO:BP homeostatic process 1922 47
GO:BP alpha-amino acid catabolic process 80 7
GO:BP regulation of vasculature development 310 14
GO:BP cellular detoxification 108 8
GO:BP response to oxygen-containing compound 1820 45
GO:BP androgen biosynthetic process 8 3
GO:BP ribosomal small subunit assembly 20 4
GO:BP regulation of cellular amide metabolic process 438 17
GO:BP cellular process 17828 272
GO:BP cellular aldehyde metabolic process 59 6
GO:BP response to insulin 284 13
GO:BP nucleoside metabolic process 61 6
GO:BP secondary metabolic process 61 6
GO:BP NADPH oxidation 9 3
GO:BP long-chain fatty acid metabolic process 115 8
GO:BP cellular response to toxic substance 115 8
GO:BP response to oxygen radical 22 4
GO:BP response to superoxide 22 4
GO:BP nucleobase-containing small molecule metabolic process 537 19
GO:BP angiogenesis 545 19
GO:BP liver regeneration 42 5
GO:BP response to drug 459 17
GO:BP animal organ regeneration 91 7
GO:BP lipid catabolic process 335 14
GO:BP negative regulation of cell adhesion mediated by integrin 10 3
GO:BP positive regulation of establishment of protein localization to telomere 10 3
GO:BP regulation of translation 377 15
GO:BP cellular amino acid catabolic process 92 7
GO:BP androgen metabolic process 24 4
GO:BP membrane lipid metabolic process 187 10
GO:BP detoxification 123 8
GO:BP blood vessel development 743 23
GO:BP drug metabolic process 68 6
GO:BP localization 6168 114
GO:BP regulation of establishment of protein localization to telomere 11 3
GO:BP kynurenine metabolic process 11 3
GO:BP ribosomal large subunit biogenesis 69 6
GO:BP anatomical structure formation involved in morphogenesis 1165 31
GO:BP tube morphogenesis 911 26
GO:BP lactation 72 6
GO:BP maturation of LSU-rRNA 27 4
GO:BP estrogen metabolic process 27 4
GO:BP regulation of establishment of protein localization to chromosome 12 3
GO:BP response to organic substance 3418 70
GO:BP regulation of endocannabinoid signaling pathway 3 2
GO:BP positive regulation of cell cycle phase transition 102 7
GO:BP positive regulation of DNA biosynthetic process 74 6
GO:BP vasculature development 773 23
GO:BP icosanoid metabolic process 134 8
GO:BP response to oxidative stress 447 16
GO:BP cellular hormone metabolic process 135 8
GO:BP ncRNA processing 363 14
GO:BP mammary gland development 170 9
GO:BP positive regulation of protein localization to chromosome, telomeric region 13 3
GO:BP monoacylglycerol metabolic process 13 3
GO:BP response to peptide hormone 452 16
GO:BP tube development 1137 30
GO:BP cell death 2136 48
GO:BP prostaglandin metabolic process 52 5
GO:BP prostanoid metabolic process 52 5
GO:BP organic cyclic compound catabolic process 458 16
GO:BP sphingolipid metabolic process 140 8
GO:BP parturition 14 3
GO:BP aldehyde catabolic process 14 3
GO:BP cellular ketone metabolic process 213 10
GO:BP cellular amino acid metabolic process 253 11
GO:BP response to inorganic substance 604 19
GO:BP positive regulation of mitotic cell cycle phase transition 81 6
GO:BP glutathione derivative metabolic process 4 2
GO:BP regulation of complement activation 15 3
GO:BP nitrobenzene metabolic process 4 2
GO:BP protein localization to organelle 859 24
GO:BP negative regulation of osteoblast differentiation 56 5
GO:BP positive regulation of mitotic cell cycle 114 7
GO:BP regulation of protein localization to chromosome, telomeric region 15 3
GO:BP alpha-amino acid metabolic process 182 9
GO:BP negative regulation of endothelial cell chemotaxis 4 2
GO:BP L-kynurenine catabolic process 4 2
GO:BP glutathione derivative biosynthetic process 4 2
GO:BP response to copper ion 33 4
GO:BP cellular response to insulin stimulus 222 10
GO:BP nucleobase biosynthetic process 16 3
GO:BP aromatic amino acid family catabolic process 16 3
GO:BP ribosome localization 16 3
GO:BP formation of cytoplasmic translation initiation complex 16 3
GO:BP establishment of protein localization to telomere 16 3
GO:BP establishment of localization 4658 88
GO:BP ribosomal subunit export from nucleus 16 3
GO:BP reactive oxygen species metabolic process 225 10
GO:BP steroid metabolic process 306 12
GO:BP cytoplasmic translational initiation 35 4
GO:BP response to peptide 531 17
GO:BP programmed cell death 1975 44
GO:BP cellular response to peptide hormone stimulus 309 12
GO:BP apoptotic process 1919 43
GO:BP cellular response to vascular endothelial growth factor stimulus 60 5
GO:BP system development 4876 91
GO:BP rRNA-containing ribonucleoprotein complex export from nucleus 17 3
GO:BP glutamine family amino acid biosynthetic process 17 3
GO:BP translational initiation 121 7
GO:BP response to organic cyclic compound 1043 27
GO:BP body fluid secretion 123 7
GO:BP alpha-amino acid biosynthetic process 62 5
GO:BP cellular amino acid biosynthetic process 62 5
GO:BP ncRNA metabolic process 449 15
GO:BP activation of membrane attack complex 5 2
GO:BP arginine biosynthetic process 5 2
GO:BP iron ion transport 63 5
GO:BP viral translational termination-reinitiation 5 2
GO:BP fatty acid beta-oxidation using acyl-CoA oxidase 5 2
GO:BP removal of superoxide radicals 18 3
GO:BP protein sulfation 5 2
GO:CC cytoplasm 11093 242
GO:CC intracellular anatomical structure 14111 262
GO:CC cytosolic ribosome 112 19
GO:CC ribosome 236 25
GO:CC ribosomal subunit 200 23
GO:CC cytosol 3849 110
GO:CC intracellular organelle 12510 234
GO:CC organelle 12827 235
GO:CC small ribosomal subunit 79 13
GO:CC intracellular membrane-bounded organelle 11363 214
GO:CC cytosolic small ribosomal subunit 45 10
GO:CC membrane-bounded organelle 11812 215
GO:CC ribonucleoprotein complex 725 32
GO:CC endomembrane system 4006 96
GO:CC endoplasmic reticulum 1761 54
GO:CC cytosolic large ribosomal subunit 64 9
GO:CC mitochondrion 1827 52
GO:CC organelle membrane 3076 75
GO:CC large ribosomal subunit 126 11
GO:CC organelle subcompartment 1580 46
GO:CC polysomal ribosome 32 6
GO:CC endoplasmic reticulum membrane 993 32
GO:CC endoplasmic reticulum subcompartment 999 32
GO:CC nuclear outer membrane-endoplasmic reticulum membrane network 1018 32
GO:CC polysome 70 7
GO:CC mitochondrial envelope 736 24
GO:CC organelle envelope 1176 33
GO:CC envelope 1176 33
GO:CC chaperonin-containing T-complex 10 3
GO:CC mitochondrial intermembrane space 99 7
GO:CC myelin sheath 206 10
GO:CC rough endoplasmic reticulum 105 7
GO:CC mitochondrial inner membrane 451 16
GO:CC synapse 1467 36
GO:CC organelle envelope lumen 111 7
GO:CC eukaryotic 48S preinitiation complex 15 3
GO:CC COP9 signalosome 34 4
GO:CC eukaryotic translation initiation factor 3 complex 16 3
GO:CC mitochondrial membrane 677 20
GO:CC eukaryotic 43S preinitiation complex 17 3
GO:CC translation preinitiation complex 18 3
GO:CC organelle inner membrane 510 16
GO:CC cellular anatomical entity 19567 288
GO:CC membrane-enclosed lumen 4582 85
GO:CC intracellular organelle lumen 4581 85
GO:CC organelle lumen 4582 85
GO:CC preribosome 74 5
GO:CC intracellular non-membrane-bounded organelle 4500 83
GO:CC preribosome, large subunit precursor 24 3
GO:CC non-membrane-bounded organelle 4515 83
GO:CC microbody 148 7
GO:CC peroxisome 148 7
GO:MF oxidoreductase activity 815 43
GO:MF structural constituent of ribosome 172 21
GO:MF rRNA binding 69 12
GO:MF catalytic activity 5665 129
GO:MF oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor 143 13
GO:MF oxidoreductase activity, acting on CH-OH group of donors 154 13
GO:MF flavin adenine dinucleotide binding 90 10
GO:MF structural molecule activity 612 25
GO:MF identical protein binding 2140 54
GO:MF lyase activity 198 12
GO:MF translation regulator activity 145 10
GO:MF anion binding 2420 58
GO:MF RNA binding 1267 36
GO:MF oligopeptide binding 17 4
GO:MF glutathione binding 17 4
GO:MF small molecule binding 2543 59
GO:MF oxidoreductase activity, acting on a sulfur group of donors 51 6
GO:MF carbonyl reductase (NADPH) activity 7 3
GO:MF NADP binding 55 6
GO:MF enzyme inhibitor activity 403 16
GO:MF oxidoreductase activity, acting on the CH-CH group of donors 60 6
GO:MF N,N-dimethylaniline monooxygenase activity 9 3
GO:MF ubiquitin ligase inhibitor activity 9 3
GO:MF site-specific endodeoxyribonuclease activity, specific for altered base 2 2
GO:MF transition metal ion binding 1064 30
GO:MF amino acid binding 63 6
GO:MF ubiquitin-protein transferase inhibitor activity 10 3
GO:MF carboxylic ester hydrolase activity 153 9
GO:MF ion binding 5862 110
GO:MF mRNA 5’-UTR binding 25 4
GO:MF protein-disulfide reductase activity 27 4
GO:MF 5.8S rRNA binding 3 2
GO:MF carbon-sulfur lyase activity 12 3
GO:MF palmitoyl-CoA oxidase activity 3 2
GO:MF 5S rRNA binding 13 3
GO:MF acylglycerol lipase activity 13 3
GO:MF nucleoside phosphate binding 2185 49
GO:MF nucleotide binding 2185 49
GO:MF translation regulator activity, nucleic acid binding 113 7
GO:MF glutathione transferase activity 33 4
GO:MF 3-hydroxy-lignoceroyl-CoA dehydratase activity 4 2
GO:MF very-long-chain 3-hydroxyacyl-CoA dehydratase activity 4 2
GO:MF 3-hydroxy-arachidoyl-CoA dehydratase activity 4 2
GO:MF 3-hydroxy-behenoyl-CoA dehydratase activity 4 2
GO:MF oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen 217 10
GO:MF steroid binding 114 7
GO:MF disulfide oxidoreductase activity 34 4
GO:MF protein folding chaperone 35 4
GO:MF hydro-lyase activity 61 5
GO:MF organic cyclic compound binding 5768 105
GO:MF oxidoreductase activity, acting on superoxide radicals as acceptor 5 2
GO:MF NAD binding 63 5
GO:MF lipase activity 124 7
GO:MF superoxide dismutase activity 5 2
GO:MF stearoyl-CoA 9-desaturase activity 5 2
GO:MF monooxygenase activity 159 8
GO:MF FAD binding 39 4
GO:MF transferase activity, transferring alkyl or aryl (other than methyl) groups 65 5
GO:MF translation factor activity, RNA binding 96 6
GO:MF complement binding 20 3
GO:MF acyl-CoA oxidase activity 6 2
GO:MF metal cluster binding 71 5
GO:MF iron-sulfur cluster binding 71 5
GO:MF ubiquitin-protein transferase regulator activity 22 3
GO:MF metalloaminopeptidase activity 22 3
HP Abnormality of metabolism/homeostasis 2240 65
KEGG Ribosome 169 21
KEGG Metabolic pathways 1563 64
KEGG Coronavirus disease - COVID-19 241 22
KEGG Biosynthesis of unsaturated fatty acids 34 7
KEGG Metabolism of xenobiotics by cytochrome P450 73 9
KEGG Fatty acid elongation 29 6
KEGG Drug metabolism - cytochrome P450 71 8
KEGG Drug metabolism - other enzymes 92 9
KEGG Biosynthesis of amino acids 78 8
KEGG Chemical carcinogenesis 101 9
KEGG Glutathione metabolism 71 7
KEGG Tryptophan metabolism 51 6
KEGG Biosynthesis of cofactors 154 10
KEGG Fatty acid metabolism 62 6
KEGG Ovarian steroidogenesis 62 6
REAC Formation of a pool of free 40S subunits 98 20
REAC Metabolism 1679 81
REAC GTP hydrolysis and joining of the 60S ribosomal subunit 109 20
REAC L13a-mediated translational silencing of Ceruloplasmin expression 108 20
REAC Eukaryotic Translation Initiation 116 20
REAC Cap-dependent Translation Initiation 116 20
REAC SRP-dependent cotranslational protein targeting to membrane 89 17
REAC Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) 91 17
REAC Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 110 17
REAC Nonsense-Mediated Decay (NMD) 110 17
REAC Translation 217 23
REAC Formation of the ternary complex, and subsequently, the 43S complex 49 12
REAC Ribosomal scanning and start codon recognition 56 12
REAC Translation initiation complex formation 56 12
REAC Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S 57 12
REAC rRNA processing 167 18
REAC Major pathway of rRNA processing in the nucleolus and cytosol 167 18
REAC rRNA processing in the nucleus and cytosol 167 18
REAC Biological oxidations 204 18
REAC FMO oxidises nucleophiles 3 3
REAC Metabolism of lipids 573 29
REAC Phase II - Conjugation of compounds 91 10
REAC Fatty acid metabolism 169 13
REAC Glutathione conjugation 34 6
REAC Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) 8 3
REAC Formation of the active cofactor, UDP-glucuronate 3 2
REAC alpha-linolenic acid (ALA) metabolism 12 3
REAC alpha-linolenic (omega3) and linoleic (omega6) acid metabolism 12 3
REAC Phase I - Functionalization of compounds 107 8
TF Factor: Kaiso; motif: SARNYCTCGCGAGAN; match class: 1 9949 201
TF Factor: E2F-1; motif: GNGGGCGGGRMN 14228 254
TF Factor: ZF5; motif: GSGCGCGR 14821 258
TF Factor: FOXN4; motif: NNWANNCGWMCGCGTCNNNNMT; match class: 1 12768 233
TF Factor: AhR; motif: NTNGCGTGNNN 3488 93
TF Factor: ELK-1; motif: ACCGGAWRTN 14697 255
TF Factor: E2F-4; motif: NTTTCSCGCC 10545 202
TF Factor: FOXN4; motif: NNWANNCGWMCGCGTCNNNNMT 16009 269
TF Factor: LKLF; motif: NGGGCGG 7220 153
TF Factor: Sp3; motif: AGGGCGG 7220 153
TF Factor: SP6; motif: WGGGCGG 7220 153
TF Factor: CPBP; motif: NGGGCGG 7220 153
TF Factor: ZF5; motif: NRNGNGCGCGCWN 14469 250
TF Factor: E2F; motif: GGCGSG 10391 196
TF Factor: ZF5; motif: NRNGNGCGCGCWN; match class: 1 11181 206
TF Factor: AhR:Arnt; motif: KNNKNNTYGCGTGCMS 2875 77
TF Factor: ZF5; motif: GSGCGCGR; match class: 1 12032 216
TF Factor: BEN; motif: CAGCGRNV; match class: 1 11980 215
TF Factor: Kaiso; motif: SARNYCTCGCGAGAN 13491 234
TF Factor: E2F-1; motif: GNGGGCGGGRMN; match class: 1 10601 196
TF Factor: Elk-1; motif: NNNNCCGGAARTNN 10072 188
TF Factor: Hes1; motif: NNCACGYGNN; match class: 1 11386 206
TF Factor: E2F-1; motif: NNNSSCGCSAANN 9013 173
TF Factor: Hes1; motif: NNCACGYGNN 15504 257
TF Factor: Klf17; motif: NGGGCGG 6533 135
TF Factor: AhR,; motif: NRCGTGNGN 4421 100
TF Factor: PEA3; motif: RCCGGAAGYN 9964 184
TF Factor: ZF5; motif: GYCGCGCARNGCNN 9484 177
TF Factor: AhR; motif: CCYCNRRSTNGCGTGASA 3480 82
TF Factor: SP100; motif: NNCGTCGNNTAAWNN 8478 159
TF Factor: E2F; motif: NCSCGCSAAAN 5198 109
TF Factor: E2F-4; motif: GNNGGCGGGAAN 5907 120
TF Factor: AHR; motif: CACGCN; match class: 1 2729 67
TF Factor: IRF6; motif: NNNACTCYCGGKNNN 13409 225
TF Factor: E2F-7; motif: GRGGCGGGAANNN 7914 149
TF Factor: MYF6; motif: NNNRACAGNCNCNCC; match class: 1 7012 135
TF Factor: E2F; motif: TTTSGCGSG 5455 111
TF Factor: GABP-alpha; motif: CTTCCK 10764 189
TF Factor: E2F-3; motif: GGCGGGN 11268 195
TF Factor: E2F1; motif: NNNNNGCGSSAAAN 5835 116
TF Factor: SP6; motif: WGGGCGG; match class: 1 2360 58
TF Factor: CPBP; motif: NGGGCGG; match class: 1 2360 58
TF Factor: LKLF; motif: NGGGCGG; match class: 1 2360 58
TF Factor: Sp3; motif: AGGGCGG; match class: 1 2360 58
TF Factor: ELK-1; motif: ACCGGAWRTN; match class: 1 9029 163
TF Factor: MYF6; motif: NNNRACAGNCNCNCC 14294 234
TF Factor: TEL1; motif: CNCGGAANNN 10420 182
TF Factor: BEN; motif: CWGCGAYA 6569 126
TF Factor: IRF4; motif: NNNAYTCTCGGWNNN; match class: 1 8126 149
TF Factor: AhR:Arnt; motif: GRGKATYGCGTGMCWNSCC 5815 114
TF Factor: ZF5; motif: GYCGCGCARNGCNN; match class: 1 5819 114
TF Factor: Egr-2; motif: GCGTGGGCGG 7210 135
TF Factor: BEN; motif: CAGCGRNV 16234 257
TF Factor: E2F-1; motif: TTTSGCGS 5974 116
TF Factor: AhR; motif: NTNGCGTGNNN; match class: 1 393 17
TF Factor: Pax-5; motif: RRMSWGANWYCTNRAGCGKRACSRYNSM 11986 202
TF Factor: RNF96; motif: BCCCGCRGCC 6337 121
TF Factor: c-Myc:Max; motif: GCCAYGYGSN; match class: 1 2409 57
TF Factor: Pax-3; motif: NNNNNNCGTCACGSTYNNNNN 12917 214
TF Factor: HES-1; motif: GSCACGMGMC 3590 77
TF Factor: E2F-1; motif: NTTSGCGG; match class: 1 1815 46
TF Factor: p53; motif: RGRCWWGYCYNGRCWWGYYY 7799 142
TF Factor: ERG; motif: ACCGGAART 9550 167
TF Factor: E2F-1; motif: TTTSGCGCGMNR 5994 114
TF Factor: ZBED6; motif: NRRGCTCGCCNN 5544 107
TF Factor: AhR; motif: NNNKNGCGTGNSNNNNN 1222 34
TF Factor: SP4; motif: NNWAGGCGTGNCNNN 4923 97
TF Factor: E2F; motif: NKCGCGCSAAAN 4858 96
TF Factor: BCL6B; motif: NNNNCCGCCCCWNNNN 13664 222
TF Factor: Pax-5; motif: RRMSWGANWYCTNRAGCGKRACSRYNSM; match class: 1 5518 106
TF Factor: SP4; motif: NNKGGGCGKGNCN 1941 47
TF Factor: Ets2; motif: ACCGGAWRYN 7919 142
TF Factor: TEL1; motif: CNCGGAANNN; match class: 1 4384 88
TF Factor: E2F-4; motif: GCGGGAAANA 10318 176
TF Factor: E2F; motif: NNTTTCGCGCN 5159 100
TF Factor: Tcfl5; motif: NNCNCGNGNN 6337 118
TF Factor: Tcfl5; motif: NNCNCGNGNN; match class: 1 6337 118
TF Factor: SP1:SP3; motif: CCSCCCCCYCC 6684 123
TF Factor: NGFI-C; motif: WTGCGTGGGYGG 5000 97
TF Factor: c-ets-1; motif: ACCGGAWRYN 8408 148
TF Factor: HIC1; motif: NNNGGKTGCCCSNNNNNN 2851 62
TF Factor: HIF-1alpha; motif: NCACGT 6382 118
TF Factor: Zic1; motif: NNCCCCCGGGGGGG 9522 164
TF Factor: IRF4; motif: NNNAYTCTCGGWNNN 14544 232
TF Factor: EGR-1; motif: TGCGTGGGCGK 4136 83
TF Factor: CTCF; motif: NAGGGGGCGCNNKNNNN; match class: 1 9341 161
TF Factor: Elf-1; motif: AWCCCGGAAGTN 8375 147
TF Factor: AhR; motif: CCYCNRRSTNGCGTGASA; match class: 1 383 15
TF Factor: c-Ets-1; motif: NNNRCCGGAWRYNNNN 7309 131
TF Factor: E2F-1; motif: TTTSGCGS; match class: 1 1582 39
TF Factor: E2F-4; motif: NGGGGGCGGGRMNN 6987 126
TF Factor: Egr-3; motif: NTGCGTGGGCGK 6055 112
TF Factor: arnt; motif: CACGYA 4582 89
TF Factor: SP2; motif: GGGCGGGAC 8107 142
TF Factor: GKLF; motif: WGGGYGKGGCCN; match class: 1 3595 73
TF Factor: HIF-1alpha; motif: GNACGTGM 6619 120
TF Factor: SP2; motif: GGGCGGGAC; match class: 1 3289 68
TF Factor: GKLF; motif: GCCMCRCCCNNN 7840 138
TF Factor: AP-2alpha; motif: NGCCYSNNGSN 6174 113
TF Factor: ELF4; motif: CCCGGAARTN 7185 128
TF Factor: GKLF; motif: WGGGYGKGGCCN 8978 154
TF Factor: HES-1; motif: NNCKYGTGNNN 4062 80
TF Factor: E2F-1; motif: NNNSSCGCSAANN; match class: 1 4125 81
TF Factor: Sp1; motif: GGNGGGGGNGGGGGMGGGGCNGGG 10752 179
TF Factor: Sp1; motif: NGGGGCGGGGN 9122 156
TF Factor: E2F-4; motif: GCGGGAAANA; match class: 1 4700 90
TF Factor: Kid3; motif: CCACN; match class: 1 21165 305
TF Factor: CPBP; motif: SNCCCNN; match class: 1 19929 294
TF Factor: AP-2; motif: SNNNCCNCAGGCN 7085 126
TF Factor: ZBED6; motif: NRRGCTCGCCNN; match class: 1 1364 34
TF Factor: ctcf; motif: CCNCNAGRKGGCRSTN 5575 103
TF Factor: Erm; motif: NCCGGAWGTN 5268 98
TF Factor: SP100; motif: NNCGTCGNNTAAWNN; match class: 1 3060 63
TF Factor: c-Myc:Max; motif: GCCAYGYGSN 7338 129
TF Factor: MAF; motif: GCTGAGTCAN 6937 123
TF Factor: AP-2; motif: MKCCCSCNGGCG 8029 139
TF Factor: E2F-3; motif: GGCGGGN; match class: 1 6875 122
TF Factor: ER71; motif: ACCGGAARYN 4325 83
TF Factor: Egr-2; motif: NTGCGTRGGCGK 5359 99
TF Factor: AP-2beta; motif: GCNNNGGSCNGVGGGN 5101 95
TF Factor: E2F-4; motif: NTTTCSCGCC; match class: 1 5364 99
TF Factor: AHR; motif: CACGCN 8469 145
TF Factor: AP-2gamma; motif: GCCYNCRGSN 7106 125
TF Factor: Zscan2; motif: GTCAAAACGC 59 5
TF Factor: E2F; motif: TTTSGCGSG 4808 90
TF Factor: BTEB2; motif: RGGGNGKGGN 7600 132
TF Factor: GKLF; motif: NNNRGGNGNGGSN 15302 238
TF Factor: Pet-1; motif: GCNGGAAGYG 13321 212
TF Factor: IRF6; motif: NNNACTCYCGGKNNN; match class: 1 7128 125
TF Factor: SAP-1a; motif: NRRCCGGAAGYRN 9134 154
TF Factor: Kaiso; motif: GCMGGGRGCRGS 11131 182
TF Factor: REST; motif: KTCAGCACCAYGGACAGCKCCN 7904 136
TF Factor: E2F-1; motif: NKTSSCGC 7904 136
TF Factor: Elk-1; motif: NCCGGAAGTGN 14565 228
TF Factor: Egr-2; motif: GCGTGGGCGG; match class: 1 2774 57
TF Factor: WT1; motif: SMCNCCNSC 8128 139
TF Factor: GABPalpha_GABPbeta; motif: CTTCCKGY 2969 60
TF Factor: Pax-3; motif: NNNNNNCGTCACGSTYNNNNN; match class: 1 6178 110
TF Factor: GKLF; motif: GCCMCRCCCNNN; match class: 1 2968 60
TF Factor: LRH-1; motif: NYCAAGGYCAN; match class: 1 411 14
WP Cytoplasmic Ribosomal Proteins 81 17
WP Metapathway biotransformation 141 12
WP Estrogen metabolism 14 4
WP Omega-3/Omega-6 FA synthesis 15 4
WP Translation Factors 49 6
WP Selenium Micronutrient Network 23 4
WP Folic Acid Network 23 4
WP Oxidative Stress and Redox Pathway 93 8
WP Tryptophan metabolism 44 5
WP Omega-9 FA synthesis 14 3
WP Oxidative Stress 28 4

2.2.7 Functional Enrichment - Kidney Ahr Regulated

kable(Kidney_Ahr_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size), 
      table.attr = "class=\"striped\"", format = "html")
source term_name term_size intersection_size
CORUM Parvulin-associated pre-rRNP complex 46 7
GO:BP small molecule metabolic process 1713 82
GO:BP organic acid metabolic process 944 53
GO:BP oxoacid metabolic process 908 51
GO:BP carboxylic acid metabolic process 896 50
GO:BP cellular amino acid metabolic process 253 24
GO:BP alpha-amino acid metabolic process 182 20
GO:BP cellular amide metabolic process 1077 47
GO:BP organonitrogen compound biosynthetic process 1570 58
GO:BP organonitrogen compound metabolic process 6326 142
GO:BP lipid metabolic process 1344 51
GO:BP small molecule catabolic process 346 24
GO:BP metabolic process 11429 211
GO:BP catabolic process 2399 72
GO:BP organic substance catabolic process 1985 63
GO:BP organic substance metabolic process 10989 204
GO:BP small molecule biosynthetic process 617 31
GO:BP obsolete oxidation-reduction process 548 29
GO:BP cellular metabolic process 10350 194
GO:BP carboxylic acid catabolic process 221 18
GO:BP organic acid catabolic process 228 18
GO:BP anion transport 529 27
GO:BP monocarboxylic acid metabolic process 616 29
GO:BP organic anion transport 372 22
GO:BP cellular lipid metabolic process 994 38
GO:BP primary metabolic process 10243 189
GO:BP peptide metabolic process 835 34
GO:BP sulfur compound metabolic process 317 20
GO:BP amide biosynthetic process 793 32
GO:BP hormone metabolic process 219 16
GO:BP cellular catabolic process 2059 58
GO:BP cellular modified amino acid metabolic process 179 14
GO:BP organic hydroxy compound metabolic process 527 24
GO:BP nucleobase-containing small molecule metabolic process 537 24
GO:BP fatty acid metabolic process 425 21
GO:BP organic acid biosynthetic process 290 17
GO:BP carboxylic acid transport 297 17
GO:BP monocarboxylic acid transport 121 11
GO:BP lipid catabolic process 335 18
GO:BP alpha-amino acid biosynthetic process 62 8
GO:BP carboxylic acid biosynthetic process 282 16
GO:BP cellular amino acid biosynthetic process 62 8
GO:BP biosynthetic process 5882 118
GO:BP nitrogen compound metabolic process 9669 173
GO:BP nucleotide metabolic process 466 21
GO:BP nucleoside phosphate metabolic process 476 21
GO:BP translation 657 25
GO:BP monocarboxylic acid catabolic process 122 10
GO:BP regulation of biological quality 3876 84
GO:BP peptide biosynthetic process 677 25
GO:BP L-serine biosynthetic process 4 3
GO:BP alpha-amino acid catabolic process 80 8
GO:BP organic substance biosynthetic process 5779 113
GO:BP nucleotide biosynthetic process 229 13
GO:BP nucleoside phosphate biosynthetic process 232 13
GO:BP organonitrogen compound catabolic process 1249 36
GO:BP steroid metabolic process 306 15
GO:BP alcohol metabolic process 344 16
GO:BP cellular amino acid catabolic process 92 8
GO:BP cellular lipid catabolic process 214 12
GO:BP organophosphate metabolic process 891 28
GO:BP detoxification 123 9
GO:BP NAD biosynthetic process 16 4
GO:BP serine family amino acid biosynthetic process 16 4
GO:BP cholesterol biosynthetic process 50 6
GO:BP secondary alcohol biosynthetic process 50 6
GO:BP fatty acid catabolic process 99 8
GO:BP cellular biosynthetic process 5715 109
GO:BP cytoplasmic translation 101 8
GO:BP cellular hormone metabolic process 135 9
GO:BP sulfur compound biosynthetic process 106 8
GO:BP sterol biosynthetic process 56 6
GO:BP pyridine nucleotide biosynthetic process 20 4
GO:BP cellular nitrogen compound metabolic process 6201 115
GO:BP serine family amino acid metabolic process 37 5
GO:BP nicotinamide nucleotide biosynthetic process 20 4
GO:BP acetyl-CoA metabolic process 37 5
GO:BP L-serine metabolic process 8 3
GO:BP secondary alcohol metabolic process 141 9
GO:BP transmembrane transport 1533 39
GO:BP purine-containing compound metabolic process 406 16
GO:BP fatty acid oxidation 114 8
GO:BP organophosphate biosynthetic process 500 18
GO:BP lipid localization 459 17
GO:BP amine metabolic process 119 8
GO:BP pyridine-containing compound biosynthetic process 23 4
GO:BP lipid oxidation 120 8
GO:BP ion transport 1572 39
GO:BP lipid biosynthetic process 647 21
GO:BP aspartate family amino acid metabolic process 43 5
GO:BP regulation of hormone levels 559 19
GO:BP negative regulation of ubiquitin protein ligase activity 11 3
GO:BP thyroid hormone transport 11 3
GO:BP steroid biosynthetic process 161 9
GO:BP glutathione metabolic process 70 6
GO:BP vitamin metabolic process 70 6
GO:BP cholesterol metabolic process 129 8
GO:BP glutamine family amino acid metabolic process 71 6
GO:BP negative regulation of ERBB signaling pathway 27 4
GO:BP thyroid hormone metabolic process 27 4
GO:BP carbohydrate derivative metabolic process 975 27
GO:BP lipid transport 401 15
GO:BP astral microtubule organization 12 3
GO:BP response to toxic substance 240 11
GO:BP response to zinc ion 49 5
GO:BP carbohydrate metabolic process 587 19
GO:BP L-alanine import across plasma membrane 3 2
GO:BP alcohol biosynthetic process 136 8
GO:BP nicotinamide nucleotide metabolic process 29 4
GO:BP sterol metabolic process 137 8
GO:BP pyridine nucleotide metabolic process 29 4
GO:BP indolalkylamine metabolic process 13 3
GO:BP tryptophan metabolic process 13 3
GO:BP short-chain fatty acid metabolic process 13 3
GO:BP water-soluble vitamin metabolic process 30 4
GO:BP aromatic amino acid family metabolic process 30 4
GO:BP ribonucleoside bisphosphate metabolic process 110 7
GO:BP cellular amine metabolic process 110 7
GO:BP purine nucleoside bisphosphate metabolic process 110 7
GO:BP nucleoside bisphosphate metabolic process 110 7
GO:BP lipid modification 218 10
GO:BP purine nucleotide metabolic process 385 14
GO:BP pyridine-containing compound metabolic process 33 4
GO:BP response to copper ion 33 4
GO:BP sulfur amino acid metabolic process 33 4
GO:BP response to metal ion 388 14
GO:BP L-alanine transmembrane transport 4 2
GO:BP terpenoid metabolic process 85 6
GO:BP N-glycan processing 16 3
GO:BP gap junction assembly 16 3
GO:BP glycine metabolic process 16 3
GO:BP formation of cytoplasmic translation initiation complex 16 3
GO:BP cytoplasmic translational initiation 35 4
GO:BP response to iron ion 36 4
GO:BP sodium-independent organic anion transport 17 3
GO:BP primary alcohol metabolic process 90 6
GO:BP glycerolipid catabolic process 62 5
GO:CC cytoplasm 11093 219
GO:CC cytosolic ribosome 112 14
GO:CC cytosol 3849 95
GO:CC cytosolic small ribosomal subunit 45 9
GO:CC intracellular anatomical structure 14111 234
GO:CC ribosomal subunit 200 15
GO:CC small ribosomal subunit 79 10
GO:CC brush border 134 12
GO:CC ribosome 236 15
GO:CC cluster of actin-based cell projections 193 13
GO:CC brush border membrane 73 8
GO:CC intracellular organelle 12510 205
GO:CC organelle 12827 208
GO:CC intracellular membrane-bounded organelle 11363 189
GO:CC membrane-bounded organelle 11812 194
GO:CC endomembrane system 4006 83
GO:CC cellular anatomical entity 19567 280
GO:CC endoplasmic reticulum 1761 44
GO:CC mitochondrion 1827 45
GO:CC organelle envelope 1176 32
GO:CC envelope 1176 32
GO:CC ribonucleoprotein complex 725 23
GO:CC eukaryotic translation initiation factor 3 complex, eIF3e 2 2
GO:CC organelle membrane 3076 64
GO:CC eukaryotic translation elongation factor 1 complex 3 2
GO:CC basal part of cell 291 12
GO:CC mitochondrial matrix 341 13
GO:CC basal plasma membrane 272 11
GO:CC nuclear envelope 460 15
GO:CC cytosolic large ribosomal subunit 64 5
GO:CC vacuole 562 17
GO:CC lytic vacuole 468 15
GO:CC lysosome 468 15
GO:CC apical part of cell 474 15
GO:CC apical plasma membrane 388 13
GO:CC polysome 70 5
GO:CC cell junction 2071 43
GO:CC collagen network 7 2
GO:CC network-forming collagen trimer 7 2
GO:CC collagen type IV trimer 7 2
GO:CC basement membrane collagen trimer 7 2
GO:MF catalytic activity 5665 135
GO:MF oxidoreductase activity 815 35
GO:MF structural constituent of ribosome 172 14
GO:MF rRNA binding 69 9
GO:MF 5S rRNA binding 13 5
GO:MF identical protein binding 2140 57
GO:MF transporter activity 1137 37
GO:MF organic acid transmembrane transporter activity 156 12
GO:MF carboxylic acid transmembrane transporter activity 155 12
GO:MF flavin adenine dinucleotide binding 90 9
GO:MF secondary active transmembrane transporter activity 232 14
GO:MF transmembrane transporter activity 1053 34
GO:MF monocarboxylic acid transmembrane transporter activity 56 7
GO:MF anion transmembrane transporter activity 295 15
GO:MF lyase activity 198 12
GO:MF dipeptidase activity 15 4
GO:MF amide binding 367 16
GO:MF active transmembrane transporter activity 346 15
GO:MF carbon-carbon lyase activity 55 6
GO:MF metallodipeptidase activity 8 3
GO:MF organic anion transmembrane transporter activity 172 10
GO:MF RNA binding 1267 34
GO:MF asparaginase activity 2 2
GO:MF ubiquitin ligase inhibitor activity 9 3
GO:MF ubiquitin-protein transferase inhibitor activity 10 3
GO:MF transferase activity, transferring alkyl or aryl (other than methyl) groups 65 6
GO:MF single-stranded RNA binding 92 7
GO:MF structural molecule activity 612 20
GO:MF mRNA 5’-UTR binding 25 4
GO:MF acyl-CoA dehydrogenase activity 11 3
GO:MF small molecule binding 2543 55
GO:MF oleic acid binding 3 2
GO:MF D5 dopamine receptor binding 3 2
GO:MF carbon-nitrogen lyase activity 13 3
GO:MF hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides 77 6
GO:MF symporter activity 140 8
GO:MF vitamin binding 141 8
GO:MF inorganic anion transmembrane transporter activity 142 8
GO:MF NADP binding 55 5
GO:MF translation regulator activity 145 8
GO:MF translation regulator activity, nucleic acid binding 113 7
GO:MF glutathione disulfide oxidoreductase activity 4 2
GO:MF hormone binding 85 6
GO:MF sodium-independent organic anion transmembrane transporter activity 16 3
GO:MF binding 14895 229
GO:MF carboxylic ester hydrolase activity 153 8
GO:MF hydrolase activity, acting on ester bonds 735 21
GO:MF oxidoreductase activity, acting on the CH-CH group of donors 60 5
GO:MF carboxy-lyase activity 36 4
GO:MF intramolecular oxidoreductase activity, transposing C=C bonds 17 3
GO:MF lipase activity 124 7
GO:MF protein binding 10189 166
GO:MF AMP binding 18 3
GO:MF long-chain-acyl-CoA dehydrogenase activity 5 2
GO:MF aminoacylase activity 5 2
GO:MF exopeptidase activity 96 6
GO:MF translation factor activity, RNA binding 96 6
GO:MF RNA polymerase II general transcription initiation factor binding 19 3
GO:MF carboxypeptidase activity 41 4
GO:MF sialyltransferase activity 20 3
GO:MF peptide binding 290 11
GO:MF lysophospholipase activity 20 3
GO:MF acetyl-CoA C-acetyltransferase activity 6 2
GO:MF steroid delta-isomerase activity 6 2
GO:MF alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity 6 2
GO:MF ubiquitin-protein transferase regulator activity 22 3
GO:MF general transcription initiation factor binding 45 4
GO:MF mRNA binding 394 13
HP Abnormal radial artery morphology 18 5
HP Elevated red cell adenosine deaminase level 18 5
HP Radial artery aplasia 18 5
HP Macrocytic dyserythropoietic anemia 19 5
HP Macrocytic anemia 58 8
HP Thrombocytosis 46 7
HP Abnormal circulating serine concentration 5 3
HP Increased mean corpuscular volume 35 6
HP Malignant genitourinary tract tumor 22 5
HP Adenocarcinoma of the colon 23 5
HP Erythroid hypoplasia 21 5
HP Pure red cell aplasia 23 5
HP Nonimmune hydrops fetalis 38 6
HP Abnormal enzyme/coenzyme activity 477 22
HP Persistence of hemoglobin F 25 5
HP Adenocarcinoma of the large intestine 26 5
HP Abnormality of the thenar eminence 25 5
HP Osteomalacia 26 5
HP Abnormal erythrocyte enzyme level 26 5
HP Osteosarcoma 28 5
HP Normochromic anemia 29 5
HP Reticulocytopenia 29 5
HP Abnormal mean corpuscular volume 45 6
HP Increased lactate dehydrogenase level 31 5
HP Adenocarcinoma of the intestines 31 5
HP Hypoglycinemia 2 2
HP Duplication of thumb phalanx 49 6
HP Elevated 8(9)-cholestenol 2 2
HP Elevated 8-dehydrocholesterol 2 2
HP Partial duplication of thumb phalanx 33 5
HP Abnormal number of erythroid precursors 34 5
HP Abnormal platelet count 351 17
HP Systemic lupus erythematosus 34 5
HP Neoplasm of the gastrointestinal tract 261 14
HP Partial duplication of the phalanx of hand 35 5
HP Rickets 36 5
KEGG Metabolic pathways 1563 66
KEGG Ribosome 169 14
KEGG Coronavirus disease - COVID-19 241 16
KEGG Steroid biosynthesis 20 5
KEGG Glutathione metabolism 71 8
KEGG Glycine, serine and threonine metabolism 39 6
KEGG Glyoxylate and dicarboxylate metabolism 31 5
REAC GTP hydrolysis and joining of the 60S ribosomal subunit 109 18
REAC L13a-mediated translational silencing of Ceruloplasmin expression 108 18
REAC Eukaryotic Translation Initiation 116 18
REAC Cap-dependent Translation Initiation 116 18
REAC Translation initiation complex formation 56 13
REAC Ribosomal scanning and start codon recognition 56 13
REAC Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S 57 13
REAC Formation of a pool of free 40S subunits 98 16
REAC Formation of the ternary complex, and subsequently, the 43S complex 49 12
REAC Metabolism 1679 70
REAC SRP-dependent cotranslational protein targeting to membrane 89 14
REAC Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) 91 14
REAC Translation 217 20
REAC Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 110 14
REAC Nonsense-Mediated Decay (NMD) 110 14
REAC Metabolism of amino acids and derivatives 234 18
REAC Major pathway of rRNA processing in the nucleolus and cytosol 167 15
REAC rRNA processing in the nucleus and cytosol 167 15
REAC rRNA processing 167 15
REAC Sialic acid metabolism 30 6
REAC SLC-mediated transmembrane transport 218 15
REAC Synthesis of substrates in N-glycan biosythesis 58 7
REAC Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein 68 7
REAC Biological oxidations 204 12
REAC ARL13B-mediated ciliary trafficking of INPP5E 3 2
REAC Cholesterol biosynthesis 25 4
REAC Metabolism of nucleotides 91 7
REAC Cholesterol biosynthesis via desmosterol 4 2
REAC Cholesterol biosynthesis via lathosterol 4 2
REAC Metabolism of RNA 532 21
TF Factor: E2F-1; motif: GNGGGCGGGRMN 14228 235
TF Factor: BEN; motif: CAGCGRNV 16234 256
TF Factor: FOXN4; motif: NNWANNCGWMCGCGTCNNNNMT 16009 253
TF Factor: Hes1; motif: NNCACGYGNN 15504 244
TF Factor: Mxi1; motif: NCACGTGGSNGNNNN 3073 69
TF Factor: USF2; motif: NNNCCACGTGACN 3892 82
TF Factor: Hes1; motif: NNCACGYGNN; match class: 1 11386 191
TF Factor: ZF5; motif: GSGCGCGR 14821 234
TF Factor: GKLF; motif: NNNRGGNGNGGSN 15302 240
TF Factor: Zfp536; motif: NCGGAKG 6308 118
TF Factor: BCL6B; motif: NNNNCCGCCCCWNNNN 13664 219
TF Factor: ZF5; motif: NRNGNGCGCGCWN 14469 228
TF Factor: E2F-3; motif: GGCGGGN 11268 186
TF Factor: Kaiso; motif: SARNYCTCGCGAGAN 13491 215
TF Factor: Klf17; motif: NGGGCGG 6533 119
TF Factor: FOXN4; motif: NNWANNCGWMCGCGTCNNNNMT; match class: 1 12768 205
TF Factor: USF1; motif: NNNNGTCACGTGGN 3312 69
TF Factor: GLI; motif: NSTGGGTGGTCY 9871 166
TF Factor: BEN; motif: CAGCGRNV; match class: 1 11980 194
TF Factor: E2F-1; motif: NTTSGCGG 6957 124
TF Factor: AR; motif: GNNCNNNNTGTTCTN; match class: 1 565 19
TF Factor: c-Myc; motif: KACCACGTGSYY 5491 102
TF Factor: N-Myc; motif: NNCCACGTGNNN 4316 84
TF Factor: Egr-1; motif: WTGCGTGGGCGK 4340 84
WP Cytoplasmic Ribosomal Proteins 81 12
WP Cholesterol metabolism (includes both Bloch and Kandutsch-Russell pathways) 51 6
WP mRNA processing 444 22
WP Translation Factors 49 6
WP One carbon metabolism and related pathways 52 6
WP Amino Acid metabolism 95 8

2.2.8 Functional Enrichment - Kidney TCDD-AhR Regulated

kable(Kidney_Interx_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size), 
      table.attr = "class=\"striped\"", format = "html")
source term_name term_size intersection_size
GO:BP response to decreased oxygen levels 341 4
GO:BP tube development 1137 6
GO:BP response to organic substance 3418 9
GO:BP response to organic cyclic compound 1043 6
GO:BP response to hypoxia 326 4
GO:BP response to oxygen levels 368 4
GO:BP cellular response to oxygen levels 175 3
GO:BP regulation of B cell differentiation 30 2
GO:BP estrogen metabolic process 27 2
GO:BP enzyme linked receptor protein signaling pathway 916 5
GO:BP cellular response to hypoxia 146 3
GO:BP fatty acid metabolic process 425 4
GO:BP tube morphogenesis 911 5
GO:BP cellular response to decreased oxygen levels 156 3
GO:BP positive regulation of catabolic process 481 4
GO:BP reproductive structure development 503 4
GO:BP reproductive system development 508 4
GO:BP catabolic process 2399 7
GO:BP cellular response to organic substance 2453 7
GO:BP lipid modification 218 3
GO:BP transmembrane receptor protein tyrosine kinase signaling pathway 587 4
GO:BP negative regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation 1 1
GO:BP response to abiotic stimulus 1177 5
GO:BP tissue development 1923 6
GO:BP phytanic acid metabolic process 1 1
GO:BP response to raffinose 1 1
GO:BP epidermal growth factor receptor signaling pathway via MAPK cascade 1 1
GO:BP GDP-L-fucose salvage 1 1
GO:BP convergent extension involved in somitogenesis 1 1
GO:BP dibenzo-p-dioxin catabolic process 1 1
GO:BP circulatory system development 1174 5
GO:BP monocarboxylic acid metabolic process 616 4
GO:BP cellular response to organic cyclic compound 595 4
GO:BP blood vessel morphogenesis 647 4
GO:BP platelet-derived growth factor receptor signaling pathway 60 2
GO:BP cellular response to raffinose 1 1
GO:BP regulation of cell cycle process 599 4
GO:BP stromal-epithelial cell signaling involved in prostate gland development 1 1
GO:BP organic substance catabolic process 1985 6
GO:BP positive regulation of fat cell differentiation 67 2
GO:BP regulation of morphogenesis of an epithelium 69 2
GO:BP cellular catabolic process 2059 6
GO:BP blood vessel development 743 4
GO:BP lipid metabolic process 1344 5
GO:BP cellular response to chemical stimulus 3097 7
GO:BP ERK1 and ERK2 cascade 344 3
GO:BP vasculature development 773 4
GO:BP MAPK cascade 771 4
GO:BP head development 805 4
GO:BP regulation of epithelial cell proliferation 359 3
GO:BP insecticide metabolic process 2 1
GO:BP small molecule catabolic process 346 3
GO:BP regulation of planar cell polarity pathway involved in axis elongation 2 1
GO:BP negative regulation of planar cell polarity pathway involved in axis elongation 2 1
GO:BP Wnt signaling pathway involved in dorsal/ventral axis specification 2 1
GO:BP regulation of Wnt signaling pathway involved in dorsal/ventral axis specification 2 1
GO:BP negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification 2 1
GO:BP canonical Wnt signaling pathway involved in regulation of type B pancreatic cell proliferation 2 1
GO:BP regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation 2 1
GO:BP septum transversum development 2 1
GO:BP proepicardium development 2 1
GO:BP oxoacid metabolic process 908 4
GO:BP vasculogenesis 90 2
GO:BP carboxylic acid metabolic process 896 4
GO:BP response to fibroblast growth factor 104 2
GO:BP cellular response to interleukin-1 103 2
GO:BP cellular response to fibroblast growth factor stimulus 97 2
GO:BP response to vitamin 103 2
GO:BP negative regulation of myeloid cell differentiation 97 2
GO:BP regulation of cell cycle 898 4
GO:BP response to chemical 5544 9
GO:BP regulation of fibroblast proliferation 102 2
GO:BP fibroblast proliferation 104 2
GO:BP positive regulation of cellular catabolic process 414 3
GO:BP GDP-L-fucose biosynthetic process 3 1
GO:BP negative regulation of B cell differentiation 3 1
GO:BP regulation of catabolic process 893 4
GO:BP positive regulation of aggrephagy 3 1
GO:BP Wnt signaling pathway involved in somitogenesis 3 1
GO:BP positive regulation of intracellular mRNA localization 3 1
GO:BP methyl-branched fatty acid metabolic process 3 1
GO:BP neural crest cell fate commitment 3 1
GO:BP fatty acid catabolic process 99 2
GO:BP lipid hydroxylation 3 1
GO:BP regulation of intracellular mRNA localization 3 1
GO:BP positive regulation of signal transduction 1506 5
GO:BP regulation of aggrephagy 3 1
GO:BP positive regulation of canonical Wnt signaling pathway 106 2
GO:BP epithelial cell proliferation 424 3
GO:BP regulation of mitotic cell cycle 425 3
GO:BP organic acid metabolic process 944 4
GO:BP fatty acid oxidation 114 2
GO:BP response to 2,3,7,8-tetrachlorodibenzodioxine 4 1
GO:BP lipid oxidation 120 2
GO:BP monocarboxylic acid catabolic process 122 2
GO:BP cellular lipid metabolic process 994 4
GO:BP cellular response to heparin 4 1
GO:BP dibenzo-p-dioxin metabolic process 4 1
GO:BP axis elongation involved in somitogenesis 4 1
GO:BP GDP-L-fucose metabolic process 4 1
GO:BP female gonad development 123 2
GO:BP development of primary female sexual characteristics 128 2
GO:BP regulation of midbrain dopaminergic neuron differentiation 5 1
GO:BP regulation of myeloid leukocyte differentiation 125 2
GO:BP small molecule metabolic process 1713 5
GO:BP animal organ development 3617 7
GO:BP canonical Wnt signaling pathway involved in regulation of cell proliferation 5 1
GO:BP stem cell fate commitment 5 1
GO:BP planar cell polarity pathway involved in axis elongation 5 1
GO:BP response to nematode 5 1
GO:BP reproduction 1775 5
GO:BP response to interleukin-1 131 2
GO:BP phosphatidylinositol 3-kinase signaling 127 2
GO:BP reproductive process 1774 5
GO:BP response to heparin 5 1
GO:BP positive regulation of Wnt signaling pathway 136 2
GO:BP positive regulation of cell communication 1725 5
GO:BP positive regulation of hyaluronan biosynthetic process 5 1
GO:BP nuclear-transcribed mRNA catabolic process, deadenylation-independent decay 5 1
GO:BP fatty acid beta-oxidation using acyl-CoA oxidase 5 1
GO:BP positive regulation of signaling 1732 5
GO:BP cellular hormone metabolic process 135 2
GO:BP digestive tract development 137 2
GO:BP female sex differentiation 143 2
GO:BP cell cycle process 1082 4
GO:BP gland development 513 3
GO:BP regulation of fat cell differentiation 142 2
GO:BP system development 4876 8
GO:BP anatomical structure morphogenesis 2715 6
GO:BP prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis 6 1
GO:BP negative regulation of non-canonical Wnt signaling pathway 6 1
GO:BP coumarin metabolic process 6 1
GO:BP B cell differentiation 147 2
GO:BP phenylpropanoid metabolic process 6 1
GO:BP response to iron(III) ion 6 1
GO:BP regulation of branching involved in prostate gland morphogenesis 6 1
GO:BP prostate glandular acinus morphogenesis 6 1
GO:BP epithelial tube formation 151 2
GO:BP digestive system development 152 2
GO:BP positive regulation of biological process 6305 9
GO:BP obsolete oxidation-reduction process 548 3
GO:BP fatty acid alpha-oxidation 7 1
GO:BP 9-cis-retinoic acid metabolic process 7 1
GO:BP phosphatidylinositol-mediated signaling 162 2
GO:BP regulation of biological quality 3876 7
GO:BP keratinocyte apoptotic process 7 1
GO:BP regulation of keratinocyte apoptotic process 7 1
GO:BP regulation of hormone levels 559 3
GO:BP 9-cis-retinoic acid biosynthetic process 7 1
GO:BP tube formation 163 2
GO:BP epithelium development 1171 4
GO:BP inositol lipid-mediated signaling 165 2
GO:BP placenta development 172 2
GO:BP positive regulation of neurotrophin TRK receptor signaling pathway 8 1
GO:BP regulation of dopaminergic neuron differentiation 8 1
GO:BP aggrephagy 8 1
GO:BP regulation of epithelial tube formation 8 1
GO:BP positive regulation of epithelial tube formation 8 1
GO:BP chorio-allantoic fusion 8 1
GO:BP response to herbicide 8 1
GO:BP developmental process involved in reproduction 1191 4
GO:BP convergent extension involved in axis elongation 8 1
GO:BP regulation of lymphocyte differentiation 178 2
GO:BP positive regulation of protein localization to early endosome 9 1
GO:BP regulation of hyaluronan biosynthetic process 9 1
GO:BP regulation of protein localization to early endosome 9 1
GO:BP positive regulation of peroxisome proliferator activated receptor signaling pathway 9 1
GO:BP neural tube development 181 2
GO:BP positive regulation of fibroblast apoptotic process 9 1
GO:BP maternal process involved in parturition 9 1
GO:BP response to nutrient 187 2
GO:BP cell population proliferation 2072 5
GO:BP negative regulation of fibroblast apoptotic process 10 1
GO:BP convergent extension involved in gastrulation 10 1
GO:BP monocarboxylic acid biosynthetic process 194 2
GO:BP positive regulation of execution phase of apoptosis 10 1
GO:BP positive regulation of monocyte differentiation 10 1
GO:BP positive regulation of cerebellar granule cell precursor proliferation 11 1
GO:BP protein mono-ADP-ribosylation 11 1
GO:BP mesendoderm development 11 1
GO:BP negative regulation of erythrocyte differentiation 11 1
GO:BP diterpenoid biosynthetic process 11 1
GO:BP neural crest formation 11 1
GO:BP cellular response to tumor necrosis factor 198 2
GO:BP cellular response to steroid hormone stimulus 205 2
GO:BP protein localization to early endosome 11 1
GO:BP morphogenesis of a branching epithelium 203 2
GO:BP positive regulation of epithelial cell proliferation 205 2
GO:BP prostate glandular acinus development 11 1
GO:BP response to stimulus 9950 11
GO:BP bone trabecula formation 11 1
GO:BP dorsal/ventral axis specification 11 1
GO:BP retinoic acid biosynthetic process 11 1
GO:BP multicellular organism development 5441 8
GO:BP cellular lipid catabolic process 214 2
GO:BP regulation of protein localization to endosome 14 1
GO:BP flavonoid metabolic process 14 1
GO:BP organic acid catabolic process 228 2
GO:BP morphogenesis of a branching structure 220 2
GO:BP myeloid leukocyte differentiation 219 2
GO:BP regulation of myeloid cell differentiation 217 2
GO:BP activation of cysteine-type endopeptidase activity 14 1
GO:BP positive regulation of extrinsic apoptotic signaling pathway via death domain receptors 13 1
GO:BP establishment or maintenance of transmembrane electrochemical gradient 12 1
GO:BP mitotic cell cycle process 666 3
GO:BP planar cell polarity pathway involved in neural tube closure 12 1
GO:BP negative regulation of platelet-derived growth factor receptor signaling pathway 13 1
GO:BP midbrain dopaminergic neuron differentiation 14 1
GO:BP regulation of establishment of planar polarity involved in neural tube closure 13 1
GO:BP hormone metabolic process 219 2
GO:BP positive regulation of cell cycle process 224 2
GO:BP positive regulation of response to stimulus 2198 5
GO:BP nucleotide salvage 14 1
GO:BP sodium ion export across plasma membrane 14 1
GO:BP negative regulation of secretion 207 2
GO:BP stress-activated MAPK cascade 231 2
GO:BP regulation of MAPK cascade 708 3
GO:BP protein kinase B signaling 214 2
GO:BP branching involved in prostate gland morphogenesis 13 1
GO:BP carboxylic acid catabolic process 221 2
GO:BP response to tumor necrosis factor 223 2
GO:BP regulation of Wnt signaling pathway, planar cell polarity pathway 14 1
GO:BP bone trabecula morphogenesis 14 1
GO:BP establishment of planar polarity involved in neural tube closure 14 1
GO:BP protein auto-ADP-ribosylation 12 1
GO:BP positive regulation of protein localization to endosome 13 1
GO:BP regulation of type B pancreatic cell proliferation 14 1
GO:BP parturition 14 1
GO:BP response to insecticide 13 1
GO:BP regulation of cerebellar granule cell precursor proliferation 14 1
GO:BP cellular response to transforming growth factor beta stimulus 231 2
GO:BP positive regulation of ERK1 and ERK2 cascade 225 2
GO:BP cellular response to X-ray 12 1
GO:BP cellular response to salt stress 14 1
GO:BP cellular potassium ion homeostasis 13 1
GO:BP cellular response to growth factor stimulus 669 3
GO:BP hyaluronan biosynthetic process 14 1
GO:BP positive regulation of epidermal growth factor-activated receptor activity 13 1
GO:BP positive regulation of non-canonical Wnt signaling pathway 14 1
GO:BP response to growth factor 697 3
GO:BP positive regulation of protein catabolic process 225 2
GO:BP intracellular mRNA localization 12 1
GO:BP positive regulation of developmental process 1412 4
GO:BP response to transforming growth factor beta 235 2
GO:BP skeletal system morphogenesis 237 2
GO:BP cellular response to prostaglandin E stimulus 15 1
GO:BP negative regulation of JUN kinase activity 15 1
GO:BP xenobiotic catabolic process 15 1
GO:BP nucleotide-sugar biosynthetic process 16 1
GO:BP cellular metabolic process 10350 11
GO:BP establishment of planar polarity of embryonic epithelium 16 1
GO:BP developmental growth 739 3
GO:BP regulation of B cell activation 248 2
GO:BP regulation of neurotrophin TRK receptor signaling pathway 16 1
GO:BP regulation of multicellular organismal development 1444 4
GO:BP convergent extension 16 1
GO:BP negative regulation of osteoblast proliferation 16 1
GO:BP regulation of canonical Wnt signaling pathway 241 2
GO:BP 3’-UTR-mediated mRNA destabilization 16 1
GO:BP regulation of cellular catabolic process 745 3
GO:BP stress-activated protein kinase signaling cascade 246 2
GO:BP intracellular receptor signaling pathway 244 2
GO:BP positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay 16 1
GO:BP regulation of peroxisome proliferator activated receptor signaling pathway 16 1
GO:BP fat cell differentiation 247 2
GO:MF hydroperoxy icosatetraenoate dehydratase activity 7 2
GO:MF fucokinase activity 1 1
GO:MF hydro-lyase activity 61 2
GO:MF flavonoid 3’-monooxygenase activity 1 1
GO:MF lyase activity 198 3
GO:MF pristanoyl-CoA oxidase activity 1 1
GO:MF prostaglandin-I synthase activity 1 1
GO:MF carbon-oxygen lyase activity 78 2
GO:MF vitamin D 24-hydroxylase activity 2 1
GO:MF P-type potassium:proton transporter activity 3 1
GO:MF estrogen 2-hydroxylase activity 3 1
GO:MF ion binding 5862 9
GO:MF oxidoreductase activity, acting on the CH-CH group of donors, oxygen as acceptor 9 1
GO:MF oxidoreductase activity, acting on diphenols and related substances as donors 7 1
GO:MF heme binding 183 2
GO:MF thiamine pyrophosphate binding 8 1
GO:MF tetrapyrrole binding 192 2
GO:MF metal ion binding 4043 7
GO:MF P-type sodium transporter activity 9 1
GO:MF P-type sodium:potassium-exchanging transporter activity 9 1
GO:MF acyl-CoA oxidase activity 6 1
GO:MF monooxygenase activity 159 2
GO:MF P-type potassium transmembrane transporter activity 11 1
GO:MF cation binding 4138 7
GO:MF iron ion binding 211 2
GO:MF estrogen 16-alpha-hydroxylase activity 12 1
GO:MF oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen 217 2
GO:MF P-type proton-exporting transporter activity 15 1
GO:MF protein ADP-ribosylase activity 15 1
GO:MF heterocyclic compound binding 5672 8
GO:MF sulfur compound binding 256 2
GO:MF organic cyclic compound binding 5768 8
REAC Fatty acid metabolism 169 4
REAC Peroxisomal lipid metabolism 27 2
REAC Sterols are 12-hydroxylated by CYP8B1 1 1
REAC Cytochrome P450 - arranged by substrate type 71 2
REAC Peroxisomal protein import 61 2
REAC Metabolism of lipids 573 4
REAC Arachidonic acid metabolism 61 2
REAC Biosynthesis of protectins 3 1
WP Eicosanoid metabolism via Cyclo Oxygenases (COX) 31 2

2.2.9 Functional Enrichment - Liver and Kidney Ahr Regulated

kable(TissueIntersect_Ahr_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size), 
      table.attr = "class=\"striped\"", format = "html")
source term_name term_size intersection_size
GO:BP oxoacid metabolic process 908 11
GO:BP carboxylic acid metabolic process 896 11
GO:BP organic acid metabolic process 944 11
GO:BP cellular amino acid metabolic process 253 7
GO:BP small molecule metabolic process 1713 13
GO:BP cellular modified amino acid metabolic process 179 5
GO:BP response to copper ion 33 3
GO:BP hormone metabolic process 219 5
GO:BP stress response to copper ion 6 2
GO:BP detoxification of copper ion 6 2
GO:BP detoxification 123 4
GO:BP transition metal ion homeostasis 136 4
GO:BP detoxification of inorganic compound 9 2
GO:BP stress response to metal ion 11 2
GO:BP alpha-amino acid metabolic process 182 4
GO:BP obsolete oxidation-reduction process 548 6
GO:BP cellular response to zinc ion 15 2
GO:BP NAD biosynthetic process 16 2
GO:BP nicotinamide nucleotide biosynthetic process 20 2
GO:BP pyridine nucleotide biosynthetic process 20 2
GO:BP carboxylic acid catabolic process 221 4
GO:BP cellular response to copper ion 20 2
GO:BP organic acid catabolic process 228 4
GO:BP response to toxic substance 240 4
GO:BP pyridine-containing compound biosynthetic process 23 2
GO:BP cellular transition metal ion homeostasis 109 3
GO:BP metal ion homeostasis 685 6
GO:BP nitric oxide mediated signal transduction 26 2
GO:BP thyroid hormone metabolic process 27 2
GO:BP cellular zinc ion homeostasis 28 2
GO:BP pyridine nucleotide metabolic process 29 2
GO:BP nicotinamide nucleotide metabolic process 29 2
GO:BP aromatic amino acid family metabolic process 30 2
GO:BP zinc ion homeostasis 30 2
GO:BP carboxylic acid biosynthetic process 282 4
GO:BP pyridine-containing compound metabolic process 33 2
GO:BP cation homeostasis 755 6
GO:BP cellular response to cadmium ion 33 2
GO:BP organic acid biosynthetic process 290 4
GO:BP response to D-galactose 1 1
GO:BP iron ion export across plasma membrane 1 1
GO:BP inorganic ion homeostasis 768 6
GO:BP N-acetylmannosamine metabolic process 1 1
GO:BP spleen trabecula formation 1 1
GO:BP mannosamine metabolic process 1 1
GO:MF oxidoreductase activity 815 9
GO:MF hormone binding 85 3
GO:MF steroid hormone receptor activity 18 2
GO:MF catalytic activity 5665 18
GO:MF argininosuccinate lyase activity 1 1
GO:MF arylformamidase activity 1 1
GO:MF butyryl-CoA dehydrogenase activity 2 1
GO:MF iodide peroxidase activity 2 1
GO:MF malic enzyme activity 3 1
GO:MF malate dehydrogenase (decarboxylating) (NAD+) activity 3 1
GO:MF malate dehydrogenase (decarboxylating) (NADP+) activity 3 1
GO:MF nicotinate-nucleotide diphosphorylase (carboxylating) activity 3 1
GO:MF thyroxine 5’-deiodinase activity 3 1
GO:MF oxidoreductase activity, acting on phosphorus or arsenic in donors 2 1
GO:MF isovaleryl-CoA dehydrogenase activity 1 1
GO:MF oxidoreductase activity, acting on phosphorus or arsenic in donors, disulfide as acceptor 2 1
GO:MF glutathione dehydrogenase (ascorbate) activity 2 1
GO:MF type 1 metabotropic glutamate receptor binding 2 1
GO:MF thyroxine 5-deiodinase activity 3 1
GO:MF hormone-sensitive lipase activity 2 1
GO:MF estrogen response element binding 3 1
GO:MF triglyceride binding 3 1
GO:MF oxidoreductase activity, acting on a sulfur group of donors, quinone or similar compound as acceptor 3 1
GO:MF acireductone dioxygenase [iron(II)-requiring] activity 1 1
GO:MF transition metal ion binding 1064 7
GO:MF cysteine-S-conjugate N-acetyltransferase activity 1 1
GO:MF fructose transmembrane transporter activity 3 1
GO:MF N-acylglucosamine 2-epimerase activity 1 1
GO:MF methylarsonate reductase activity 2 1
GO:MF all-trans-retinol 13,14-reductase activity 1 1
GO:MF oxidoreductase activity, acting on the CH-CH group of donors, with a flavin as acceptor 3 1
GO:MF oxidoreductase activity, acting on the CH-CH group of donors 60 2
GO:MF nicotinamide phosphoribosyltransferase activity 1 1
GO:MF copper ion binding 65 2
GO:MF TFIIB-class transcription factor binding 4 1
GO:MF N-acetyl-beta-D-galactosaminidase activity 4 1
GO:MF acetylesterase activity 4 1
GO:MF ferrous iron transmembrane transporter activity 4 1
GO:MF glutathione disulfide oxidoreductase activity 4 1
GO:MF oxaloacetate decarboxylase activity 4 1
GO:MF hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides 77 2
GO:MF estrogen receptor activity 5 1
GO:MF aminoacylase activity 5 1
GO:MF short-chain carboxylesterase activity 5 1
KEGG Mineral absorption 53 3

2.2.10 Functional Enrichment - Liver-specific Ahr Regulated

kable(Diff_Liver_Ahr_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size), 
      table.attr = "class=\"striped\"", format = "html")
source term_name term_size intersection_size
GO:BP small molecule metabolic process 1713 120
GO:BP organic acid metabolic process 944 81
GO:BP carboxylic acid metabolic process 896 77
GO:BP oxoacid metabolic process 908 77
GO:BP monocarboxylic acid metabolic process 616 55
GO:BP lipid metabolic process 1344 79
GO:BP metabolic process 11429 304
GO:BP cellular lipid metabolic process 994 60
GO:BP small molecule biosynthetic process 617 46
GO:BP fatty acid metabolic process 425 37
GO:BP cellular catabolic process 2059 91
GO:BP organic acid biosynthetic process 290 30
GO:BP catabolic process 2399 100
GO:BP obsolete oxidation-reduction process 548 41
GO:BP cellular metabolic process 10350 276
GO:BP alpha-amino acid metabolic process 182 23
GO:BP carboxylic acid catabolic process 221 25
GO:BP carboxylic acid biosynthetic process 282 28
GO:BP small molecule catabolic process 346 31
GO:BP organic acid catabolic process 228 25
GO:BP cellular amino acid metabolic process 253 26
GO:BP organonitrogen compound metabolic process 6326 190
GO:BP cellular amino acid catabolic process 92 16
GO:BP organic substance catabolic process 1985 83
GO:BP organic substance metabolic process 10989 283
GO:BP hormone metabolic process 219 22
GO:BP alpha-amino acid catabolic process 80 14
GO:BP response to hormone 912 48
GO:BP carbohydrate derivative metabolic process 975 49
GO:BP organic hydroxy compound metabolic process 527 33
GO:BP generation of precursor metabolites and energy 446 30
GO:BP regulation of hormone levels 559 34
GO:BP cellular hormone metabolic process 135 16
GO:BP steroid metabolic process 306 24
GO:BP response to oxygen-containing compound 1820 71
GO:BP sulfur compound metabolic process 317 24
GO:BP organophosphate metabolic process 891 44
GO:BP lipid biosynthetic process 647 36
GO:BP alpha-amino acid biosynthetic process 62 11
GO:BP response to endogenous stimulus 1619 65
GO:BP primary metabolic process 10243 256
GO:BP alcohol metabolic process 344 24
GO:BP regulation of biological quality 3876 119
GO:BP regulation of lipid metabolic process 361 24
GO:BP triglyceride metabolic process 112 13
GO:BP monocarboxylic acid biosynthetic process 194 17
GO:BP organic substance transport 2416 83
GO:BP unsaturated fatty acid metabolic process 133 14
GO:BP localization 6168 169
GO:BP transport 4502 132
GO:BP response to organonitrogen compound 1093 47
GO:BP cellular modified amino acid metabolic process 179 16
GO:BP establishment of localization 4658 135
GO:BP response to external stimulus 2912 94
GO:BP carbohydrate metabolic process 587 31
GO:BP drug metabolic process 68 10
GO:BP protein catabolic process in the vacuole 18 6
GO:BP acylglycerol metabolic process 143 14
GO:BP neutral lipid metabolic process 145 14
GO:BP nucleobase-containing small molecule metabolic process 537 29
GO:BP response to nitrogen compound 1199 49
GO:BP cellular ketone metabolic process 213 17
GO:BP monosaccharide metabolic process 266 19
GO:BP response to wounding 517 28
GO:BP response to drug 459 26
GO:BP response to stress 3817 114
GO:BP liver development 173 15
GO:BP response to organic cyclic compound 1043 44
GO:BP positive regulation of lipid metabolic process 174 15
GO:BP hexose metabolic process 247 18
GO:BP hepaticobiliary system development 176 15
GO:BP liver morphogenesis 32 7
GO:BP regulation of small molecule metabolic process 355 22
GO:BP ribose phosphate metabolic process 385 23
GO:BP long-chain fatty acid metabolic process 115 12
GO:BP organonitrogen compound biosynthetic process 1570 58
GO:BP monosaccharide biosynthetic process 96 11
GO:BP nucleoside phosphate metabolic process 476 26
GO:BP cellular amino acid biosynthetic process 62 9
GO:BP phosphate-containing compound metabolic process 2809 89
GO:BP organonitrogen compound catabolic process 1249 49
GO:BP cellular carbohydrate metabolic process 310 20
GO:BP regulation of hydrolase activity 1183 47
GO:BP response to organic substance 3418 103
GO:BP phosphorus metabolic process 2832 89
GO:BP tyrosine metabolic process 14 5
GO:BP regulation of inflammatory response 347 21
GO:BP cellular process 17828 383
GO:BP aspartate family amino acid catabolic process 15 5
GO:BP wound healing 380 22
GO:BP cellular response to hormone stimulus 600 29
GO:BP cellular response to chemical stimulus 3097 94
GO:BP lysosomal protein catabolic process 16 5
GO:BP regulation of peptidase activity 480 25
GO:BP macromolecule localization 2897 89
GO:BP gland development 513 26
GO:BP lipid catabolic process 335 20
GO:BP regulation of glucose metabolic process 133 12
GO:BP dicarboxylic acid metabolic process 92 10
GO:BP regulation of multicellular organismal process 2788 86
GO:BP aspartate family amino acid metabolic process 43 7
GO:BP nitrogen compound transport 1986 66
GO:BP regulation of cell population proliferation 1753 60
GO:BP nucleotide metabolic process 466 24
GO:BP ribonucleotide metabolic process 376 21
GO:BP aromatic amino acid family metabolic process 30 6
GO:BP cellular amide metabolic process 1077 42
GO:BP glucose metabolic process 212 15
GO:BP hepatocyte proliferation 30 6
GO:BP epithelial cell proliferation involved in liver morphogenesis 30 6
GO:BP organophosphate biosynthetic process 500 25
GO:BP secondary alcohol metabolic process 141 12
GO:BP response to steroid hormone 352 20
GO:BP mammary gland epithelial cell proliferation 31 6
GO:BP regulation of cellular carbohydrate metabolic process 167 13
GO:BP response to lipid 980 39
GO:BP gland morphogenesis 144 12
GO:BP cell death 2136 69
GO:BP regulation of developmental process 2591 80
GO:BP nitric oxide metabolic process 82 9
GO:BP olefinic compound metabolic process 124 11
GO:BP regulation of endopeptidase activity 451 23
GO:BP response to peptide hormone 452 23
GO:BP regulation of response to stress 1254 46
GO:BP reactive nitrogen species metabolic process 84 9
GO:BP homeostatic process 1922 63
GO:BP cellular response to xenobiotic stimulus 106 10
GO:BP response to nutrient levels 523 25
GO:BP cholesterol metabolic process 129 11
GO:BP response to extracellular stimulus 559 26
GO:BP pigment metabolic process 68 8
GO:BP regulation of response to external stimulus 904 36
GO:BP response to peptide 531 25
GO:BP regeneration 232 15
GO:BP glutathione metabolic process 70 8
GO:BP arachidonic acid metabolic process 70 8
GO:BP icosanoid metabolic process 134 11
GO:BP regulation of protein exit from endoplasmic reticulum 23 5
GO:BP primary alcohol metabolic process 90 9
GO:BP hexose biosynthetic process 90 9
GO:BP positive regulation of inflammatory response 134 11
GO:BP carbohydrate biosynthetic process 209 14
GO:BP positive regulation of lipid biosynthetic process 91 9
GO:BP animal organ regeneration 91 9
GO:BP glycerolipid metabolic process 384 20
GO:BP fatty acid oxidation 114 10
GO:BP sterol metabolic process 137 11
GO:BP response to nutrient 187 13
GO:BP response to xenobiotic stimulus 115 10
GO:BP transmembrane transport 1533 52
GO:BP purine ribonucleotide metabolic process 358 19
GO:BP positive regulation of response to wounding 74 8
GO:BP triglyceride biosynthetic process 39 6
GO:BP glomerular filtration 25 5
GO:BP regulation of cell death 1740 57
GO:BP cellular response to nutrient levels 217 14
GO:BP regulation of response to wounding 165 12
GO:BP positive regulation of hydrolase activity 653 28
GO:BP cell population proliferation 2072 65
GO:BP complement activation, alternative pathway 14 4
GO:BP regulation of body fluid levels 364 19
GO:BP organic cyclic compound catabolic process 458 22
GO:BP lipid oxidation 120 10
GO:BP renal filtration 26 5
GO:BP nitric oxide biosynthetic process 77 8
GO:BP pyruvate biosynthetic process 6 3
GO:BP inflammatory response 732 30
GO:BP monocarboxylic acid catabolic process 122 10
GO:BP cellular response to extracellular stimulus 252 15
GO:BP protein exit from endoplasmic reticulum 42 6
GO:BP cellular response to endogenous stimulus 1333 46
GO:BP regulation of carbohydrate metabolic process 199 13
GO:BP programmed cell death 1975 62
GO:BP purine-containing compound metabolic process 406 20
GO:BP regulation of proteolysis 778 31
GO:BP xenobiotic metabolic process 102 9
GO:BP secondary metabolic process 61 7
GO:BP cellular response to nitrogen compound 710 29
GO:BP regulation of wound healing 126 10
GO:BP response to glucocorticoid 176 12
GO:BP negative regulation of proteolysis 379 19
GO:BP cellular response to organonitrogen compound 643 27
GO:BP regulation of defense response 575 25
GO:BP aromatic amino acid family catabolic process 16 4
GO:BP nucleoside phosphate biosynthetic process 232 14
GO:BP positive regulation of steroid hormone biosynthetic process 7 3
GO:BP cellular response to external stimulus 322 17
GO:BP nitrogen compound metabolic process 9669 227
GO:BP protein-containing complex subunit organization 1636 53
GO:BP purine nucleotide metabolic process 385 19
GO:BP cellular response to oxygen-containing compound 1247 43
GO:BP regulation of phagocytosis 108 9
GO:BP transmembrane receptor protein tyrosine kinase signaling pathway 587 25
GO:BP glycosyl compound metabolic process 86 8
GO:BP regulation of immune system process 1406 47
GO:BP regulation of epithelial cell proliferation 359 18
GO:BP intracellular transport 1409 47
GO:BP response to gonadotropin 31 5
GO:BP gluconeogenesis 87 8
GO:BP glutamate metabolic process 31 5
GO:BP acylglycerol biosynthetic process 48 6
GO:BP neutral lipid biosynthetic process 48 6
GO:BP regulation of cysteine-type endopeptidase activity involved in apoptotic process 214 13
GO:BP cellular lipid catabolic process 214 13
GO:BP lipid localization 459 21
GO:BP ketone catabolic process 18 4
GO:BP steroid biosynthetic process 161 11
GO:BP positive regulation of response to stimulus 2198 66
GO:BP protein-containing complex assembly 1462 48
GO:BP malate metabolic process 8 3
GO:BP erythrose 4-phosphate/phosphoenolpyruvate family amino acid catabolic process 8 3
GO:BP sarcosine metabolic process 2 2
GO:BP xenobiotic detoxification by transmembrane export across the plasma membrane 8 3
GO:BP L-phenylalanine catabolic process 8 3
GO:BP biosynthetic process 5882 148
GO:BP aromatic compound catabolic process 432 20
GO:BP regulation of programmed cell death 1587 51
GO:BP pyruvate metabolic process 114 9
GO:BP negative regulation of cell death 1119 39
GO:BP negative regulation of endopeptidase activity 278 15
GO:BP endoplasmic reticulum tubular network organization 19 4
GO:BP regulation of mammary gland epithelial cell proliferation 19 4
GO:BP organic anion transport 372 18
GO:BP negative regulation of cellular process 5068 130
GO:BP retinoid metabolic process 71 7
GO:BP response to corticosteroid 194 12
GO:BP lipid homeostasis 167 11
GO:BP bile acid and bile salt transport 34 5
GO:BP negative regulation of protein metabolic process 1128 39
GO:BP negative regulation of biological process 5544 140
GO:BP regulation of triglyceride metabolic process 52 6
GO:BP response to stilbenoid 20 4
GO:BP regulation of cell differentiation 1649 52
GO:BP development of secondary female sexual characteristics 9 3
GO:BP L-phenylalanine metabolic process 9 3
GO:BP regulation of response to stimulus 3851 103
GO:BP mammary gland development 170 11
GO:BP epithelial fluid transport 9 3
GO:BP erythrose 4-phosphate/phosphoenolpyruvate family amino acid metabolic process 9 3
GO:BP regulation of ERBB signaling pathway 73 7
GO:BP ion transport 1572 50
GO:BP positive regulation of defense response 256 14
GO:BP protein transport 1535 49
GO:BP negative regulation of peptidase activity 287 15
GO:BP response to oxidative stress 447 20
GO:BP regulation of protein-containing complex assembly 448 20
GO:BP protein homotetramerization 54 6
GO:BP quinone metabolic process 36 5
GO:BP positive regulation of ERBB signaling pathway 36 5
GO:BP temperature homeostasis 173 11
GO:BP system development 4876 125
GO:BP defense response 1705 53
GO:BP negative regulation of cellular protein metabolic process 1068 37
GO:BP enzyme linked receptor protein signaling pathway 916 33
GO:BP positive regulation of wound healing 55 6
GO:BP ribose phosphate biosynthetic process 175 11
GO:BP positive regulation of phagocytosis 76 7
GO:BP porphyrin-containing compound metabolic process 37 5
GO:BP serine family amino acid metabolic process 37 5
GO:BP regulation of fatty acid metabolic process 99 8
GO:BP fatty acid catabolic process 99 8
GO:BP positive regulation of biological process 6305 155
GO:BP positive regulation of sister chromatid cohesion 10 3
GO:BP diterpenoid metabolic process 77 7
GO:BP regulation of fatty acid beta-oxidation 22 4
GO:BP regulation of hepatocyte proliferation 22 4
GO:BP negative regulation of cell maturation 10 3
GO:BP negative regulation of hydrolase activity 457 20
GO:BP epithelial cell proliferation 424 19
GO:BP NADP metabolic process 38 5
GO:BP fatty acid biosynthetic process 151 10
GO:BP macrophage migration 57 6
GO:BP regulation of cysteine-type endopeptidase activity 237 13
GO:BP protein localization 2452 70
GO:BP response to toxic substance 240 13
GO:BP response to estradiol 155 10
GO:BP regulation of renal system process 40 5
GO:BP xenobiotic transport 40 5
GO:BP negative regulation of cell population proliferation 715 27
GO:BP cellular response to drug 81 7
GO:BP low-density lipoprotein particle mediated signaling 3 2
GO:BP lipoprotein particle mediated signaling 3 2
GO:BP fumarate metabolic process 3 2
GO:BP isoleucine biosynthetic process 3 2
GO:BP chylomicron remodeling 3 2
GO:BP regulation of platelet-derived growth factor receptor signaling pathway 24 4
GO:BP protein tetramerization 82 7
GO:BP cellular response to peptide 370 17
GO:BP apoptotic process 1919 57
GO:BP regulation of lipid biosynthetic process 187 11
GO:BP regulation of localization 2868 79
GO:BP cellular response to peptide hormone stimulus 309 15
GO:BP regulation of apoptotic process 1550 48
GO:BP C21-steroid hormone metabolic process 42 5
GO:BP one-carbon metabolic process 42 5
GO:BP lipid modification 218 12
GO:BP positive regulation of small molecule metabolic process 161 10
GO:BP terpenoid metabolic process 85 7
GO:BP CDP-diacylglycerol biosynthetic process 12 3
GO:BP regulation of glomerular filtration 12 3
GO:BP positive regulation of hormone biosynthetic process 12 3
GO:BP development of secondary sexual characteristics 12 3
GO:BP multicellular organism development 5441 135
GO:BP hormone biosynthetic process 63 6
GO:BP renal system process involved in regulation of systemic arterial blood pressure 26 4
GO:BP response to chemical 5544 137
GO:BP establishment of protein localization 1647 50
GO:BP regulation of blood coagulation 64 6
GO:BP regulation of gluconeogenesis 64 6
GO:BP positive regulation of transport 1005 34
GO:BP establishment of localization in cell 2031 59
GO:BP chemical homeostasis 1245 40
GO:BP lipid storage 88 7
GO:BP anatomical structure development 5987 146
GO:BP estrogen metabolic process 27 4
GO:BP regulation of cell maturation 27 4
GO:BP renal system process 113 8
GO:BP CDP-diacylglycerol metabolic process 13 3
GO:BP alditol phosphate metabolic process 13 3
GO:BP positive regulation of nuclear-transcribed mRNA poly(A) tail shortening 13 3
GO:BP formation of translation preinitiation complex 13 3
GO:BP response to folic acid 13 3
GO:BP dicarboxylic acid biosynthetic process 13 3
GO:BP fructose metabolic process 13 3
GO:BP positive regulation of protein exit from endoplasmic reticulum 13 3
GO:BP energy reserve metabolic process 89 7
GO:BP regulation of hemostasis 66 6
GO:BP regulation of transport 1871 55
GO:BP small GTPase mediated signal transduction 422 18
GO:BP tetrapyrrole metabolic process 46 5
GO:BP positive regulation of fatty acid metabolic process 46 5
GO:BP regulation of coagulation 67 6
GO:BP regulation of nitric oxide biosynthetic process 67 6
GO:BP nucleotide biosynthetic process 229 12
GO:BP anion transport 529 21
GO:BP endoplasmic reticulum tubular network membrane organization 4 2
GO:BP negative regulation of dendritic cell differentiation 4 2
GO:BP regulation of epidermal growth factor receptor signaling pathway 68 6
GO:BP response to hypoxia 326 15
GO:BP heme catabolic process 4 2
GO:BP L-ascorbic acid biosynthetic process 4 2
GO:BP response to 2,3,7,8-tetrachlorodibenzodioxine 4 2
GO:BP endoplasmic reticulum tubular network formation 4 2
GO:BP porphyrin-containing compound catabolic process 4 2
GO:BP NADP biosynthetic process 4 2
GO:BP L-kynurenine catabolic process 4 2
GO:BP regulation of erythrocyte differentiation 47 5
GO:BP pigment catabolic process 4 2
GO:BP retinol metabolic process 47 5
GO:BP organic substance biosynthetic process 5779 141
GO:BP regulation of carbohydrate biosynthetic process 117 8
GO:BP organic acid transport 327 15
GO:BP regulation of nuclear-transcribed mRNA poly(A) tail shortening 14 3
GO:BP growth hormone receptor signaling pathway 14 3
GO:BP positive regulation of immune system process 947 32
GO:BP aldehyde catabolic process 14 3
GO:BP positive regulation of molecular function 1678 50
GO:BP response to lipoprotein particle 29 4
GO:BP regulation of nitric oxide metabolic process 69 6
GO:BP regulation of interleukin-1 beta production 93 7
GO:BP positive regulation of multicellular organismal process 1555 47
GO:BP interleukin-1 beta production 93 7
GO:BP positive regulation of catalytic activity 1268 40
GO:BP immune effector process 683 25
GO:BP carboxylic acid transport 297 14
GO:BP carbohydrate derivative biosynthetic process 574 22
GO:BP vitamin metabolic process 70 6
GO:BP acyl-CoA metabolic process 94 7
GO:BP thioester metabolic process 94 7
GO:BP animal organ development 3617 94
GO:BP energy derivation by oxidation of organic compounds 300 14
GO:BP fluid transport 30 4
GO:BP exogenous drug catabolic process 49 5
GO:BP glutamine family amino acid metabolic process 71 6
GO:BP negative regulation of circadian rhythm 15 3
GO:BP regulation of cholesterol storage 15 3
GO:BP renal system process involved in regulation of blood volume 15 3
GO:BP regulation of NLRP3 inflammasome complex assembly 15 3
GO:BP branched-chain amino acid metabolic process 15 3
GO:BP developmental process 6536 156
GO:BP cellular localization 2777 75
GO:BP glucan metabolic process 72 6
GO:BP cellular glucan metabolic process 72 6
GO:BP drug catabolic process 50 5
GO:BP glycogen metabolic process 72 6
GO:BP positive regulation of response to external stimulus 404 17
GO:BP negative regulation of programmed cell death 1002 33
GO:BP positive regulation of protein-containing complex assembly 240 12
GO:BP response to growth hormone 31 4
GO:BP heme metabolic process 31 4
GO:BP detoxification 123 8
GO:BP mammary gland epithelium development 73 6
GO:BP regulation of lipase activity 73 6
GO:BP positive regulation of cell population proliferation 1045 34
GO:BP regulation of immune effector process 339 15
GO:BP alcohol catabolic process 51 5
GO:BP cellular component organization or biogenesis 6270 150
GO:BP organic hydroxy compound catabolic process 74 6
GO:BP response to decreased oxygen levels 341 15
GO:BP cellular response to lipoprotein particle stimulus 32 4
GO:BP Golgi to endosome transport 16 3
GO:BP glycine metabolic process 16 3
GO:BP regulation of lysosome organization 5 2
GO:BP negative regulation of oocyte maturation 5 2
GO:BP regulation of cellular response to insulin stimulus 75 6
GO:BP omega-hydroxylase P450 pathway 5 2
GO:BP purine-containing compound biosynthetic process 184 10
GO:BP epithelial cell proliferation involved in mammary gland duct elongation 5 2
GO:BP mammary gland branching involved in thelarche 5 2
GO:BP positive regulation of small GTPase mediated signal transduction 75 6
GO:BP cellular nitrogen compound catabolic process 411 17
GO:BP long-chain fatty acid catabolic process 5 2
GO:BP thelarche 5 2
GO:BP triglyceride transport 5 2
GO:BP acylglycerol transport 5 2
GO:BP tetrapyrrole catabolic process 5 2
GO:BP canalicular bile acid transport 5 2
GO:BP positive regulation of platelet-derived growth factor receptor signaling pathway 5 2
GO:BP branched-chain amino acid biosynthetic process 5 2
GO:BP cellular component organization 6090 146
GO:CC cytoplasm 11093 318
GO:CC organelle membrane 3076 135
GO:CC endoplasmic reticulum 1761 83
GO:CC endoplasmic reticulum membrane 993 58
GO:CC organelle subcompartment 1580 77
GO:CC endoplasmic reticulum subcompartment 999 58
GO:CC intracellular anatomical structure 14111 349
GO:CC nuclear outer membrane-endoplasmic reticulum membrane network 1018 58
GO:CC endomembrane system 4006 141
GO:CC mitochondrion 1827 80
GO:CC mitochondrial membrane 677 41
GO:CC envelope 1176 57
GO:CC organelle envelope 1176 57
GO:CC mitochondrial envelope 736 42
GO:CC intracellular membrane-bounded organelle 11363 287
GO:CC membrane-bounded organelle 11812 292
GO:CC mitochondrial inner membrane 451 29
GO:CC cellular anatomical entity 19567 416
GO:CC organelle inner membrane 510 29
GO:CC intracellular organelle 12510 300
GO:CC organelle 12827 304
GO:CC apical part of cell 474 26
GO:CC apical plasma membrane 388 23
GO:CC endosome membrane 403 22
GO:CC membrane 10122 244
GO:CC peroxisome 148 12
GO:CC microbody 148 12
GO:CC bounding membrane of organelle 1676 57
GO:CC Golgi apparatus 1449 51
GO:CC lytic vacuole 468 23
GO:CC lysosome 468 23
GO:CC vacuole 562 26
GO:CC vacuolar membrane 280 16
GO:CC vesicle membrane 833 32
GO:CC cytosol 3849 105
GO:CC lysosomal membrane 219 13
GO:CC lytic vacuole membrane 219 13
GO:CC Golgi apparatus subcompartment 746 29
GO:CC vesicle 2077 63
GO:CC plasma membrane region 1318 44
GO:CC endosome 870 32
GO:CC basal part of cell 291 15
GO:CC membrane raft 392 18
GO:CC membrane microdomain 393 18
GO:CC microvillus 106 8
GO:CC cytoplasmic vesicle 1931 58
GO:CC basal plasma membrane 272 14
GO:CC intracellular vesicle 1937 58
GO:CC brush border 134 9
GO:CC cell surface 1061 35
GO:CC brush border membrane 73 6
GO:CC recycling endosome 179 10
GO:CC endoplasmic reticulum tubular network membrane 5 2
GO:CC intracellular canaliculus 5 2
GO:CC caveola 100 7
GO:MF catalytic activity 5665 208
GO:MF oxidoreductase activity 815 56
GO:MF oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen 217 22
GO:MF monooxygenase activity 159 18
GO:MF small molecule binding 2543 92
GO:MF anion binding 2420 89
GO:MF vitamin binding 141 16
GO:MF oxidoreductase activity, acting on CH-OH group of donors 154 16
GO:MF identical protein binding 2140 77
GO:MF heme binding 183 16
GO:MF iron ion binding 211 17
GO:MF oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor 143 14
GO:MF pyridoxal phosphate binding 54 9
GO:MF vitamin B6 binding 55 9
GO:MF ion binding 5862 160
GO:MF tetrapyrrole binding 192 16
GO:MF lyase activity 198 16
GO:MF transaminase activity 22 6
GO:MF transferase activity, transferring nitrogenous groups 23 6
GO:MF hydrolase activity 2353 75
GO:MF nucleoside phosphate binding 2185 70
GO:MF nucleotide binding 2185 70
GO:MF transferase activity 2277 72
GO:MF glutathione transferase activity 33 6
GO:MF steroid hydroxylase activity 69 8
GO:MF acyltransferase activity, transferring groups other than amino-acyl groups 232 15
GO:MF aromatase activity 36 6
GO:MF acyltransferase activity 263 16
GO:MF nickel cation binding 5 3
GO:MF bile acid binding 13 4
GO:MF magnesium ion binding 218 14
GO:MF lipid transporter activity 147 11
GO:MF carboxylic acid binding 174 12
GO:MF active transmembrane transporter activity 346 18
GO:MF protein-containing complex binding 1464 49
GO:MF lipid binding 786 31
GO:MF 1-acyl-2-lysophosphatidylserine acylhydrolase activity 7 3
GO:MF phosphatidylserine 1-acylhydrolase activity 7 3
GO:MF transferase activity, transferring alkyl or aryl (other than methyl) groups 65 7
GO:MF oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen 65 7
GO:MF organic hydroxy compound transmembrane transporter activity 47 6
GO:MF L-threonine ammonia-lyase activity 2 2
GO:MF flavin adenine dinucleotide binding 90 8
GO:MF amide binding 367 18
GO:MF steroid binding 114 9
GO:MF phospholipase A1 activity 9 3
GO:MF transition metal ion binding 1064 37
GO:MF oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen 54 6
GO:MF monocarboxylic acid transmembrane transporter activity 56 6
GO:MF ATPase-coupled transmembrane transporter activity 125 9
GO:MF L-serine ammonia-lyase activity 3 2
GO:MF long-chain fatty acid omega-hydroxylase activity 3 2
GO:MF transporter activity 1137 38
GO:MF bile acid transmembrane transporter activity 23 4
GO:MF protein binding 10189 233
GO:MF purine nucleobase binding 3 2
GO:MF primary active transmembrane transporter activity 128 9
GO:MF carboxylic ester hydrolase activity 153 10
GO:MF sphingolipid delta-4 desaturase activity 3 2
GO:MF pattern recognition receptor activity 23 4
GO:MF monocarboxylic acid binding 80 7
GO:MF estrogen 2-hydroxylase activity 3 2
GO:MF oxidoreductase activity, acting on paired donors, with oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water 11 3
GO:MF N-acyltransferase activity 103 8
GO:MF serine-type peptidase activity 217 12
GO:MF carbon-sulfur lyase activity 12 3
GO:MF serine hydrolase activity 222 12
GO:MF carbohydrate derivative binding 2248 64
GO:MF alcohol dehydrogenase (NADP+) activity 27 4
GO:MF organic cyclic compound binding 5768 141
GO:MF protein homodimerization activity 676 25
GO:MF sn-1-glycerol-3-phosphate C16:0-DCA-CoA acyl transferase activity 4 2
GO:MF glycerol-3-phosphate O-acyltransferase activity 4 2
GO:MF thrombospondin receptor activity 4 2
GO:MF serine-type endopeptidase activity 202 11
GO:MF folic acid binding 14 3
GO:MF retinol binding 14 3
GO:MF organic acid binding 145 9
GO:MF ribonucleotide binding 1937 56
GO:MF steroid dehydrogenase activity 48 5
GO:MF estrogen receptor binding 49 5
GO:MF xenobiotic transmembrane transporter activity 30 4
GO:MF aldo-keto reductase (NADP) activity 30 4
GO:MF oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen 15 3
GO:MF peptide hormone binding 51 5
GO:MF binding 14895 319
GO:MF lipase activity 124 8
GO:MF hydrolase activity, acting on ester bonds 735 26
GO:MF sodium-independent organic anion transmembrane transporter activity 16 3
GO:MF nucleobase binding 5 2
GO:MF carboxylic acid transmembrane transporter activity 155 9
GO:MF ammonia-lyase activity 5 2
GO:MF neurotrophin receptor activity 5 2
GO:MF fatty acid omega-hydroxylase activity 5 2
GO:MF lipoprotein lipase activity 5 2
GO:MF oxidoreductase activity, acting on the CH-OH group of donors, oxygen as acceptor 5 2
GO:MF organic acid transmembrane transporter activity 156 9
HP Abnormal circulating metabolite concentration 1099 60
HP Autosomal recessive inheritance 2708 109
HP Abnormal circulating carboxylic acid concentration 216 22
HP Abnormality of metabolism/homeostasis 2240 90
HP Abnormal circulating amino acid concentration 121 13
KEGG Metabolic pathways 1563 102
KEGG Bile secretion 100 14
KEGG Chemical carcinogenesis 101 14
KEGG Biosynthesis of amino acids 78 11
KEGG Carbon metabolism 121 13
KEGG Cholesterol metabolism 49 8
KEGG Glycine, serine and threonine metabolism 39 7
KEGG Cysteine and methionine metabolism 52 8
KEGG Drug metabolism - cytochrome P450 71 9
KEGG Pyruvate metabolism 44 7
KEGG Metabolism of xenobiotics by cytochrome P450 73 9
KEGG Complement and coagulation cascades 92 10
KEGG Lysosome 131 12
KEGG Glycerophospholipid metabolism 98 10
KEGG Tyrosine metabolism 39 6
KEGG Glutathione metabolism 71 8
KEGG Steroid hormone biosynthesis 91 9
KEGG Peroxisome 86 8
KEGG Phenylalanine metabolism 22 4
KEGG PPAR signaling pathway 89 8
REAC Metabolism 1679 109
REAC Metabolism of amino acids and derivatives 234 26
REAC Metabolism of lipids 573 38
REAC Phenylalanine and tyrosine metabolism 10 4
REAC Bile acid and bile salt metabolism 40 7
REAC Biological oxidations 204 17
REAC Pyruvate metabolism and Citric Acid (TCA) cycle 50 7
REAC Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol 24 5
REAC Metabolism of steroids 112 11
REAC Glutamate and glutamine metabolism 13 4
REAC Heme degradation 14 4
REAC Recycling of bile acids and salts 14 4
TF Factor: GKLF; motif: NNNRGGNGNGGSN 15302 353
TF Factor: ZBP89; motif: CCCCKCCCCCNN; match class: 1 3885 117
TF Factor: GKLF; motif: NNNRGGNGNGGSN; match class: 1 10998 267
TF Factor: Egr-2; motif: GCGTGGGCGG 7210 189
TF Factor: GKLF; motif: NNRRGRRNGNSNNN 12950 301
TF Factor: Mxi1; motif: NCACGTGGSNGNNNN 3073 94
TF Factor: ZF5; motif: NRNGNGCGCGCWN 14469 327
TF Factor: FOXN4; motif: NNWANNCGWMCGCGTCNNNNMT; match class: 1 12768 294
TF Factor: Pax-4; motif: NNNNNYCACCCB 18716 398
TF Factor: Sp1; motif: GGNGGGGGNGGGGGMGGGGCNGGG 10752 255
TF Factor: ZF5; motif: GYCGCGCARNGCNN 9484 230
TF Factor: Kid3; motif: CCACN; match class: 1 21165 431
TF Factor: NF-E2; motif: CATGACTCAGCANNCN; match class: 1 47 7
TF Factor: ZFP187; motif: NNGMCCTNGTCCNYNN 2555 79
TF Factor: ZBP89; motif: CCCCKCCCCCNN 8105 201
TF Factor: E2F-4; motif: NTTTCSCGCC; match class: 1 5364 143
TF Factor: SP1:SP3; motif: CCSCCCCCYCC 6684 171
TF Factor: MAZ; motif: GGGGAGGG 8416 206
TF Factor: GKLF; motif: NNRRGRRNGNSNNN; match class: 1 8470 207
TF Factor: SP1:SP3; motif: CCSCCCCCYCC; match class: 1 3378 98
TF Factor: MAZ; motif: NKGGGAGGGGRGGR 7957 197
TF Factor: E2F-1; motif: GNGGGCGGGRMN 14228 319
TF Factor: Hes1; motif: NNCACGYGNN; match class: 1 11386 265
TF Factor: Klf15; motif: RGGGMGGRGNNGGGGGNGG 3269 95
TF Factor: BCL6B; motif: NNNNCCGCCCCWNNNN 13664 309
TF Factor: ZF5; motif: GSGCGCGR 14821 330
TF Factor: NGFI-C; motif: WTGCGTGGGYGG 5000 133
TF Factor: WT1; motif: NNGGGNGGGSGN 7486 186
TF Factor: ZF5; motif: GYCGCGCARNGCNN; match class: 1 5819 151
TF Factor: E2F-4; motif: NTTTCSCGCC 10545 248
TF Factor: Osx; motif: CCNCCCCCNNN 6158 158
TF Factor: WT1; motif: SMCNCCNSC 8128 199
TF Factor: PPAR,; motif: RGGNCAAAGGTCA 2376 73
TF Factor: c-Myc:Max; motif: NNNNNNNCACGTGNNNNNNN 7236 180
TF Factor: Arnt; motif: NNNNNRTCACGTGAYNNNNN; match class: 1 7087 177
TF Factor: PPARgamma:RXR-alpha; motif: NTRGGNCARAGGKCA; match class: 1 5253 138
TF Factor: c-Myc:Max; motif: NNNNNNNCACGTGNNNNNNN; match class: 1 7236 180
TF Factor: E2F; motif: GGCGSG 10391 244
TF Factor: Arnt; motif: NNNNNRTCACGTGAYNNNNN 7087 177
TF Factor: FOXN4; motif: NNWANNCGWMCGCGTCNNNNMT 16009 350
TF Factor: E2F-4; motif: NGGGGGCGGGRMNN 6987 174
TF Factor: BEN; motif: CAGCGRNV 16234 353
TF Factor: CKROX; motif: SCCCTCCCC 6334 160
TF Factor: E2F-3; motif: GGCGGGN 11268 260
TF Factor: STAT1; motif: NNNSANTTCCGGGAANTGNSN; match class: 1 2881 83
TF Factor: HIF-1alpha; motif: NCACGT 6382 160
TF Factor: BTEB2; motif: GNAGGGGGNGGGSSNN 4977 130
TF Factor: MAZ; motif: NKGGGAGGGGRGGR; match class: 1 4159 112
TF Factor: c-Myc:Max; motif: NNACCACGTGGTNN; match class: 1 7970 193
TF Factor: ARNTLIKE; motif: NNNSCACGTG 5261 136
TF Factor: c-Myc:Max; motif: NNACCACGTGGTNN 7970 193
TF Factor: Pax-5; motif: BCNNNRNGCANBGNTGNRTAGCSGCHNB; match class: 1 3991 108
TF Factor: E2F-4; motif: GCGGGAAANA 10318 240
TF Factor: TEL1; motif: CNCGGAANNN 10420 242
TF Factor: AhR,; motif: NRCGTGNGN 4421 117
TF Factor: Sp1; motif: NNGGGGCGGGGNN 8939 212
TF Factor: CACD; motif: CCACRCCC 10859 250
TF Factor: VDR; motif: GGGKNARNRRGGWSA; match class: 1 3798 103
TF Factor: CREB,; motif: NTGACGTNA 8122 195
TF Factor: USF2; motif: CASGYG 6304 157
TF Factor: USF2; motif: CASGYG; match class: 1 6304 157
TF Factor: Clock; motif: CNGNCACGTGNNNM 1665 53
TF Factor: AP-2beta; motif: GCNNNGGSCNGVGGGN 5101 131
TF Factor: Pax-4; motif: NNNNNYCACCCB; match class: 1 14458 318
TF Factor: E2F-4; motif: GNNGGCGGGAAN 5907 148
TF Factor: Zfp281; motif: NNCCCCCCCCCCMYC 3971 106
TF Factor: WT1; motif: NGCGGGGGGGTSMMCYN 5297 135
TF Factor: VDR; motif: GGGKNARNRRGGWSA 10051 233
TF Factor: HNF4alpha1; motif: NRGGNCAAAGGTCAN 2111 63
TF Factor: C-Myc; motif: NGCCACGTGNN 6226 154
TF Factor: bach2; motif: TGCTGAGTCAY; match class: 1 21 4
TF Factor: ZF5; motif: GSGCGCGR; match class: 1 12032 271
TF Factor: E2F-1; motif: GNGGGCGGGRMN; match class: 1 10601 243
TF Factor: SREBP-2; motif: NNGYCACNNSMN 7690 184
TF Factor: Hes1; motif: NNCACGYGNN 15504 336
TF Factor: Sp1; motif: NGGGGCGGGGN 9122 213
TF Factor: Egr-1; motif: NNGCGKGGGCGGGG; match class: 1 1160 39
TF Factor: LKLF; motif: GGGGTGGKSN 9186 214
TF Factor: HNF4; motif: TGAMCTTTGNCCN 2230 65
TF Factor: Mycn; motif: NSCACGTGGC 154 10
TF Factor: LKLF; motif: CNCCACCCS 5803 144
TF Factor: Tax/CREB; motif: GGGGGTTGACGYANA 5338 134
TF Factor: EGR-1; motif: TGCGTGGGCGK 4136 108
TF Factor: SP2; motif: GNNGGGGGCGGGGSN 7094 171
TF Factor: CTCF; motif: NAGGGGGCGCNNKNNNN 14310 313
TF Factor: Tcfl5; motif: NNCNCGNGNN; match class: 1 6337 155
TF Factor: Tcfl5; motif: NNCNCGNGNN 6337 155
TF Factor: GKLF; motif: GCCMCRCCCNNN 7840 186
TF Factor: Sp5; motif: RNGGRGGNGGRGNNGGGGGAGGRG; match class: 1 1948 58
TF Factor: Zic3; motif: NMCCCCCGGGGGGGN; match class: 1 2035 60
TF Factor: Sp1; motif: GGNGGGGGNGGGGGMGGGGCNGGG; match class: 1 7397 177
TF Factor: E2F; motif: GGCGSG; match class: 1 7016 169
TF Factor: Sp5; motif: RNGGRGGNGGRGNNGGGGGAGGRG 4848 123
TF Factor: Sp1; motif: GGGGCGGGGT 8345 196
TF Factor: AP-2alphaA; motif: ANNGCCTNAGGSNNT 5089 128
TF Factor: USF; motif: GYCACGTGNC 3536 94
TF Factor: CREM; motif: TGACGTCASYN 5755 142
TF Factor: Kaiso; motif: SARNYCTCGCGAGAN; match class: 1 9949 228
TF Factor: CPBP; motif: SNCCCNN; match class: 1 19929 411
TF Factor: Sp1; motif: GGGGCGGGGC 8654 202
TF Factor: c-Myc:Max; motif: GCCAYGYGSN 7338 175
WP Metapathway biotransformation 141 14
WP One carbon metabolism and related pathways 52 8
WP Oxidation by Cytochrome P450 40 7
WP Amino Acid metabolism 95 10
WP Retinol metabolism 39 6

2.2.11 Functional Enrichment - Kidney-specific Ahr Regulated

kable(Diff_Kidney_Ahr_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size), 
      table.attr = "class=\"striped\"", format = "html")
source term_name term_size intersection_size
CORUM Parvulin-associated pre-rRNP complex 46 7
GO:BP small molecule metabolic process 1713 72
GO:BP organic acid metabolic process 944 44
GO:BP oxoacid metabolic process 908 42
GO:BP carboxylic acid metabolic process 896 41
GO:BP organonitrogen compound biosynthetic process 1570 55
GO:BP alpha-amino acid metabolic process 182 18
GO:BP organonitrogen compound metabolic process 6326 130
GO:BP cellular amide metabolic process 1077 42
GO:BP metabolic process 11429 193
GO:BP organic substance catabolic process 1985 59
GO:BP lipid metabolic process 1344 46
GO:BP catabolic process 2399 66
GO:BP cellular amino acid metabolic process 253 19
GO:BP organic substance metabolic process 10989 186
GO:BP small molecule catabolic process 346 21
GO:BP cellular metabolic process 10350 176
GO:BP small molecule biosynthetic process 617 28
GO:BP peptide metabolic process 835 32
GO:BP amide biosynthetic process 793 31
GO:BP obsolete oxidation-reduction process 548 25
GO:BP primary metabolic process 10243 172
GO:BP anion transport 529 24
GO:BP monocarboxylic acid metabolic process 616 26
GO:BP sulfur compound metabolic process 317 18
GO:BP carboxylic acid catabolic process 221 15
GO:BP organic acid catabolic process 228 15
GO:BP organic anion transport 372 19
GO:BP cellular lipid metabolic process 994 33
GO:BP nucleobase-containing small molecule metabolic process 537 23
GO:BP cellular catabolic process 2059 52
GO:BP translation 657 25
GO:BP organic hydroxy compound metabolic process 527 22
GO:BP carboxylic acid transport 297 16
GO:BP peptide biosynthetic process 677 25
GO:BP nucleotide metabolic process 466 20
GO:BP fatty acid metabolic process 425 19
GO:BP nucleoside phosphate metabolic process 476 20
GO:BP nitrogen compound metabolic process 9669 158
GO:BP monocarboxylic acid transport 121 10
GO:BP biosynthetic process 5882 107
GO:BP alpha-amino acid catabolic process 80 8
GO:BP alcohol metabolic process 344 16
GO:BP L-serine biosynthetic process 4 3
GO:BP alpha-amino acid biosynthetic process 62 7
GO:BP cellular amino acid biosynthetic process 62 7
GO:BP organic acid biosynthetic process 290 14
GO:BP hormone metabolic process 219 12
GO:BP lipid catabolic process 335 15
GO:BP organic substance biosynthetic process 5779 103
GO:BP nucleotide biosynthetic process 229 12
GO:BP steroid metabolic process 306 14
GO:BP secondary alcohol biosynthetic process 50 6
GO:BP cholesterol biosynthetic process 50 6
GO:BP serine family amino acid biosynthetic process 16 4
GO:BP nucleoside phosphate biosynthetic process 232 12
GO:BP cytoplasmic translation 101 8
GO:BP organonitrogen compound catabolic process 1249 33
GO:BP organophosphate metabolic process 891 26
GO:BP purine-containing compound metabolic process 406 16
GO:BP sulfur compound biosynthetic process 106 8
GO:BP carboxylic acid biosynthetic process 282 13
GO:BP sterol biosynthetic process 56 6
GO:BP secondary alcohol metabolic process 141 9
GO:BP cellular biosynthetic process 5715 100
GO:BP serine family amino acid metabolic process 37 5
GO:BP acetyl-CoA metabolic process 37 5
GO:BP L-serine metabolic process 8 3
GO:BP regulation of biological quality 3876 73
GO:BP amine metabolic process 119 8
GO:BP monocarboxylic acid catabolic process 122 8
GO:BP cellular amino acid catabolic process 92 7
GO:BP lipid transport 401 15
GO:BP cellular nitrogen compound metabolic process 6201 105
GO:BP aspartate family amino acid metabolic process 43 5
GO:BP steroid biosynthetic process 161 9
GO:BP cholesterol metabolic process 129 8
GO:BP negative regulation of ubiquitin protein ligase activity 11 3
GO:BP cellular hormone metabolic process 135 8
GO:BP alcohol biosynthetic process 136 8
GO:BP sterol metabolic process 137 8
GO:BP negative regulation of ERBB signaling pathway 27 4
GO:BP purine nucleotide metabolic process 385 14
GO:BP astral microtubule organization 12 3
GO:BP cellular modified amino acid metabolic process 179 9
GO:BP cellular amine metabolic process 110 7
GO:BP L-alanine import across plasma membrane 3 2
GO:BP purine nucleoside bisphosphate metabolic process 110 7
GO:BP ribonucleoside bisphosphate metabolic process 110 7
GO:BP nucleoside bisphosphate metabolic process 110 7
GO:BP short-chain fatty acid metabolic process 13 3
GO:BP tryptophan metabolic process 13 3
GO:BP indolalkylamine metabolic process 13 3
GO:BP lipid biosynthetic process 647 19
GO:BP carbohydrate derivative metabolic process 975 25
GO:BP fatty acid oxidation 114 7
GO:BP organophosphate biosynthetic process 500 16
GO:BP organic cyclic compound catabolic process 458 15
GO:BP terpenoid metabolic process 85 6
GO:BP lipid localization 459 15
GO:BP cellular nitrogen compound catabolic process 411 14
GO:BP sulfur amino acid metabolic process 33 4
GO:BP lipid oxidation 120 7
GO:BP gap junction assembly 16 3
GO:BP glycine metabolic process 16 3
GO:BP N-glycan processing 16 3
GO:BP cytoplasmic translational initiation 35 4
GO:BP kidney development 327 12
GO:BP formation of cytoplasmic translation initiation complex 16 3
GO:BP ribonucleotide metabolic process 376 13
GO:BP NAD biosynthetic process 16 3
GO:BP primary alcohol metabolic process 90 6
GO:BP L-alanine transmembrane transport 4 2
GO:BP acyl-CoA metabolic process 94 6
GO:BP renal system development 338 12
GO:BP sodium-independent organic anion transport 17 3
GO:BP thioester metabolic process 94 6
GO:BP ribose phosphate metabolic process 385 13
GO:BP ion transport 1572 34
GO:BP oligosaccharide metabolic process 38 4
GO:BP cellular biogenic amine metabolic process 97 6
GO:BP negative regulation of ubiquitin-protein transferase activity 18 3
GO:BP inorganic anion transport 171 8
GO:BP triglyceride transport 5 2
GO:BP negative regulation of protein neddylation 5 2
GO:BP acylglycerol transport 5 2
GO:BP cellular ketone metabolic process 213 9
GO:BP fatty acid catabolic process 99 6
GO:BP cellular lipid catabolic process 214 9
GO:BP deoxyribonucleoside monophosphate catabolic process 19 3
GO:BP purine nucleobase metabolic process 19 3
GO:BP acetyl-CoA biosynthetic process 19 3
GO:CC cytoplasm 11093 199
GO:CC cytosolic ribosome 112 14
GO:CC cytosolic small ribosomal subunit 45 9
GO:CC intracellular anatomical structure 14111 213
GO:CC ribosomal subunit 200 15
GO:CC small ribosomal subunit 79 10
GO:CC cytosol 3849 83
GO:CC ribosome 236 15
GO:CC brush border 134 11
GO:CC cluster of actin-based cell projections 193 12
GO:CC intracellular organelle 12510 186
GO:CC cellular anatomical entity 19567 254
GO:CC organelle 12827 189
GO:CC ribonucleoprotein complex 725 23
GO:CC brush border membrane 73 7
GO:CC intracellular membrane-bounded organelle 11363 170
GO:CC membrane-bounded organelle 11812 175
GO:CC endoplasmic reticulum 1761 40
GO:CC eukaryotic translation initiation factor 3 complex, eIF3e 2 2
GO:CC mitochondrion 1827 40
GO:CC endomembrane system 4006 72
GO:CC eukaryotic translation elongation factor 1 complex 3 2
GO:CC organelle envelope 1176 28
GO:CC envelope 1176 28
GO:CC mitochondrial matrix 341 12
GO:CC cytosolic large ribosomal subunit 64 5
GO:CC intracellular non-membrane-bounded organelle 4500 76
GO:CC non-membrane-bounded organelle 4515 76
GO:CC nuclear envelope 460 14
GO:CC polysome 70 5
GO:CC organelle membrane 3076 55
GO:CC collagen network 7 2
GO:CC collagen type IV trimer 7 2
GO:CC basement membrane collagen trimer 7 2
GO:CC network-forming collagen trimer 7 2
GO:MF catalytic activity 5665 121
GO:MF structural constituent of ribosome 172 14
GO:MF rRNA binding 69 9
GO:MF 5S rRNA binding 13 5
GO:MF oxidoreductase activity 815 29
GO:MF identical protein binding 2140 49
GO:MF flavin adenine dinucleotide binding 90 8
GO:MF transporter activity 1137 32
GO:MF RNA binding 1267 34
GO:MF organic acid transmembrane transporter activity 156 10
GO:MF dipeptidase activity 15 4
GO:MF carboxylic acid transmembrane transporter activity 155 10
GO:MF secondary active transmembrane transporter activity 232 12
GO:MF transmembrane transporter activity 1053 29
GO:MF amide binding 367 15
GO:MF monocarboxylic acid transmembrane transporter activity 56 6
GO:MF structural molecule activity 612 20
GO:MF anion transmembrane transporter activity 295 13
GO:MF metallodipeptidase activity 8 3
GO:MF asparaginase activity 2 2
GO:MF single-stranded RNA binding 92 7
GO:MF ubiquitin ligase inhibitor activity 9 3
GO:MF lyase activity 198 10
GO:MF ubiquitin-protein transferase inhibitor activity 10 3
GO:MF mRNA 5’-UTR binding 25 4
GO:MF vitamin binding 141 8
GO:MF inorganic anion transmembrane transporter activity 142 8
GO:MF active transmembrane transporter activity 346 13
GO:MF D5 dopamine receptor binding 3 2
GO:MF oleic acid binding 3 2
GO:MF translation regulator activity 145 8
GO:MF translation regulator activity, nucleic acid binding 113 7
GO:MF carbon-carbon lyase activity 55 5
GO:MF small molecule binding 2543 50
GO:MF binding 14895 208
GO:MF sodium-independent organic anion transmembrane transporter activity 16 3
GO:MF intramolecular oxidoreductase activity, transposing C=C bonds 17 3
GO:MF exopeptidase activity 96 6
GO:MF translation factor activity, RNA binding 96 6
GO:MF transferase activity, transferring alkyl or aryl (other than methyl) groups 65 5
GO:MF mRNA binding 394 13
GO:MF actin binding 443 14
GO:MF AMP binding 18 3
GO:MF organic anion transmembrane transporter activity 172 8
GO:MF protein binding 10189 151
GO:MF long-chain-acyl-CoA dehydrogenase activity 5 2
GO:MF carboxypeptidase activity 41 4
GO:MF sialyltransferase activity 20 3
GO:MF lysophospholipase activity 20 3
GO:MF acetyl-CoA C-acetyltransferase activity 6 2
GO:MF anion binding 2420 46
GO:MF hydrolase activity 2353 45
GO:MF alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity 6 2
GO:MF hydrolase activity, acting on ester bonds 735 19
GO:MF steroid delta-isomerase activity 6 2
GO:MF lipid transporter activity 147 7
GO:MF ubiquitin-protein transferase regulator activity 22 3
GO:MF hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides 77 5
GO:MF anion:anion antiporter activity 23 3
GO:MF thyroid hormone binding 7 2
GO:MF carboxylic ester hydrolase activity 153 7
GO:MF dopamine receptor binding 24 3
HP Elevated red cell adenosine deaminase level 18 5
HP Abnormal radial artery morphology 18 5
HP Macrocytic anemia 58 8
HP Macrocytic dyserythropoietic anemia 19 5
HP Thrombocytosis 46 7
HP Radial artery aplasia 18 5
HP Erythroid hypoplasia 21 5
HP Increased mean corpuscular volume 35 6
HP Malignant genitourinary tract tumor 22 5
HP Pure red cell aplasia 23 5
HP Adenocarcinoma of the colon 23 5
HP Nonimmune hydrops fetalis 38 6
HP Abnormal circulating serine concentration 5 3
HP Persistence of hemoglobin F 25 5
HP Abnormality of the thenar eminence 25 5
HP Abnormal erythrocyte enzyme level 26 5
HP Adenocarcinoma of the large intestine 26 5
HP Osteosarcoma 28 5
HP Abnormal mean corpuscular volume 45 6
HP Normochromic anemia 29 5
HP Reticulocytopenia 29 5
HP Increased lactate dehydrogenase level 31 5
HP Adenocarcinoma of the intestines 31 5
HP Duplication of thumb phalanx 49 6
HP Elevated 8(9)-cholestenol 2 2
HP Hypoglycinemia 2 2
HP Abnormal number of erythroid precursors 34 5
HP Partial duplication of thumb phalanx 33 5
HP Elevated 8-dehydrocholesterol 2 2
HP Systemic lupus erythematosus 34 5
HP Partial duplication of the phalanx of hand 35 5
HP Abnormal platelet count 351 16
HP Antinuclear antibody positivity 37 5
HP Horseshoe kidney 80 7
HP Cleft soft palate 160 10
HP Gastrointestinal carcinoma 64 6
HP EEG with central epileptiform discharges 3 2
HP Bilateral perisylvian polymicrogyria 3 2
HP Nephritis 60 6
HP Thrombocytopenia 333 15
HP Body odor 3 2
HP Glomerular basement membrane lamellation 3 2
HP Malar rash 11 3
HP Absent thumb 43 5
HP Acute myeloid leukemia 63 6
HP Perisylvian predominant thick cortex pachygyria 3 2
HP Thin glomerular basement membrane 3 2
HP Oral aversion 3 2
HP Abnormal enzyme/coenzyme activity 477 19
HP Hyposerinemia 3 2
HP Malignant gastrointestinal tract tumors 64 6
HP EEG with parietal focal spikes 3 2
HP EEG with central focal spikes 3 2
HP Abnormal reticulocyte morphology 64 6
HP Neoplasm of the gastrointestinal tract 261 13
KEGG Metabolic pathways 1563 58
KEGG Ribosome 169 14
KEGG Coronavirus disease - COVID-19 241 16
KEGG Steroid biosynthesis 20 5
KEGG Glycine, serine and threonine metabolism 39 6
KEGG Glyoxylate and dicarboxylate metabolism 31 5
KEGG Glutathione metabolism 71 6
REAC GTP hydrolysis and joining of the 60S ribosomal subunit 109 18
REAC L13a-mediated translational silencing of Ceruloplasmin expression 108 18
REAC Cap-dependent Translation Initiation 116 18
REAC Eukaryotic Translation Initiation 116 18
REAC Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S 57 13
REAC Formation of a pool of free 40S subunits 98 16
REAC Ribosomal scanning and start codon recognition 56 13
REAC Translation initiation complex formation 56 13
REAC Formation of the ternary complex, and subsequently, the 43S complex 49 12
REAC SRP-dependent cotranslational protein targeting to membrane 89 14
REAC Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) 91 14
REAC Translation 217 20
REAC Nonsense-Mediated Decay (NMD) 110 14
REAC Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 110 14
REAC Metabolism 1679 60
REAC Major pathway of rRNA processing in the nucleolus and cytosol 167 15
REAC rRNA processing 167 15
REAC rRNA processing in the nucleus and cytosol 167 15
REAC Sialic acid metabolism 30 6
REAC Metabolism of amino acids and derivatives 234 15
REAC Synthesis of substrates in N-glycan biosythesis 58 6
REAC SLC-mediated transmembrane transport 218 12
REAC Metabolism of RNA 532 21
REAC Cholesterol biosynthesis 25 4
REAC ARL13B-mediated ciliary trafficking of INPP5E 3 2
REAC Metabolism of nucleotides 91 7
REAC Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein 68 6
REAC Cholesterol biosynthesis via desmosterol 4 2
REAC Transport of inorganic cations/anions and amino acids/oligopeptides 96 7
REAC Cholesterol biosynthesis via lathosterol 4 2
TF Factor: E2F-1; motif: GNGGGCGGGRMN 14228 213
TF Factor: BEN; motif: CAGCGRNV 16234 231
TF Factor: USF2; motif: NNNCCACGTGACN 3892 76
TF Factor: FOXN4; motif: NNWANNCGWMCGCGTCNNNNMT 16009 226
TF Factor: Hes1; motif: NNCACGYGNN; match class: 1 11386 172
WP Cytoplasmic Ribosomal Proteins 81 12
WP mRNA processing 444 22
WP Translation Factors 49 6
WP One carbon metabolism and related pathways 52 6
WP Cholesterol metabolism (includes both Bloch and Kandutsch-Russell pathways) 51 6

2.2.12 Functional Enrichment - Liver and Kidney TCDD-AhR Regulated

kable(TissueIntersect_Interx_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size), 
      table.attr = "class=\"striped\"", format = "html")
source term_name term_size intersection_size
GO:BP estrogen metabolic process 27 2
GO:BP cellular hormone metabolic process 135 2
GO:BP dibenzo-p-dioxin catabolic process 1 1
GO:BP hormone metabolic process 219 2
GO:BP insecticide metabolic process 2 1
GO:BP phenylpropanoid metabolic process 6 1
GO:BP response to nematode 5 1
GO:BP coumarin metabolic process 6 1
GO:BP dibenzo-p-dioxin metabolic process 4 1
GO:BP response to iron(III) ion 6 1
GO:BP response to 2,3,7,8-tetrachlorodibenzodioxine 4 1
GO:BP lipid hydroxylation 3 1
GO:BP steroid metabolic process 306 2
GO:BP 9-cis-retinoic acid biosynthetic process 7 1
GO:BP 9-cis-retinoic acid metabolic process 7 1
GO:BP positive regulation of neurotrophin TRK receptor signaling pathway 8 1
GO:BP response to herbicide 8 1
GO:BP response to insecticide 13 1
GO:BP parturition 14 1
GO:BP xenobiotic catabolic process 15 1
GO:BP cellular response to organic cyclic compound 595 2
GO:BP terpenoid biosynthetic process 17 1
GO:BP diterpenoid biosynthetic process 11 1
GO:BP regulation of hormone levels 559 2
GO:BP protein mono-ADP-ribosylation 11 1
GO:BP activation of cysteine-type endopeptidase activity 14 1
GO:BP retinoic acid biosynthetic process 11 1
GO:BP flavonoid metabolic process 14 1
GO:BP transmembrane receptor protein tyrosine kinase signaling pathway 587 2
GO:BP toxin metabolic process 17 1
GO:BP regulation of neurotrophin TRK receptor signaling pathway 16 1
GO:BP maternal process involved in parturition 9 1
GO:BP cellular response to organic substance 2453 3
GO:BP protein auto-ADP-ribosylation 12 1
GO:BP hydrogen peroxide biosynthetic process 18 1
GO:BP hepatocyte differentiation 19 1
GO:BP cellular response to copper ion 20 1
GO:BP response to vitamin A 22 1
GO:BP cellular response to chemical stimulus 3097 3
GO:BP androgen metabolic process 24 1
GO:BP response to hyperoxia 25 1
GO:BP retinoic acid metabolic process 27 1
GO:BP smooth muscle tissue development 28 1
GO:BP response to iron ion 36 1
GO:BP response to immobilization stress 33 1
GO:BP face morphogenesis 34 1
GO:BP positive regulation of G1/S transition of mitotic cell cycle 36 1
GO:BP isoprenoid biosynthetic process 33 1
GO:BP neurotrophin TRK receptor signaling pathway 31 1
GO:BP response to copper ion 33 1
GO:BP response to arsenic-containing substance 35 1
GO:BP response to organic substance 3418 3
GO:BP response to increased oxygen levels 32 1
GO:BP protein ADP-ribosylation 35 1
GO:BP porphyrin-containing compound metabolic process 37 1
GO:BP enzyme linked receptor protein signaling pathway 916 2
GO:BP head morphogenesis 40 1
GO:BP dendrite extension 43 1
GO:BP neurotrophin signaling pathway 43 1
GO:BP regulation of biological quality 3876 3
GO:BP response to food 45 1
GO:BP tetrapyrrole metabolic process 46 1
GO:BP retinol metabolic process 47 1
GO:BP positive regulation of cell cycle G1/S phase transition 48 1
GO:BP response to organic cyclic compound 1043 2
GO:BP hydrogen peroxide metabolic process 51 1
GO:BP face development 52 1
GO:BP body morphogenesis 54 1
GO:BP reactive oxygen species biosynthetic process 56 1
GO:BP tube development 1137 2
GO:BP response to antibiotic 59 1
GO:BP platelet-derived growth factor receptor signaling pathway 60 1
GO:BP secondary metabolic process 61 1
GO:BP DNA methylation 64 1
GO:BP DNA alkylation 64 1
GO:BP cell differentiation 4378 3
GO:BP cellular developmental process 4454 3
GO:BP zymogen activation 66 1
GO:BP demethylation 68 1
GO:BP drug metabolic process 68 1
GO:BP retinoid metabolic process 71 1
GO:BP diterpenoid metabolic process 77 1
GO:MF flavonoid 3’-monooxygenase activity 1 1
GO:MF estrogen 2-hydroxylase activity 3 1
GO:MF vitamin D 24-hydroxylase activity 2 1
GO:MF oxidoreductase activity, acting on diphenols and related substances as donors 7 1
GO:MF hydroperoxy icosatetraenoate dehydratase activity 7 1
GO:MF estrogen 16-alpha-hydroxylase activity 12 1
GO:MF protein ADP-ribosylase activity 15 1
GO:MF NAD+ ADP-ribosyltransferase activity 23 1
GO:MF aromatase activity 36 1
GO:MF demethylase activity 40 1
GO:MF oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen 54 1
GO:MF Hsp90 protein binding 45 1
GO:MF arachidonic acid monooxygenase activity 42 1
GO:MF Hsp70 protein binding 51 1
GO:MF pentosyltransferase activity 52 1
GO:MF hydro-lyase activity 61 1
GO:MF oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen 65 1
GO:MF steroid hydroxylase activity 69 1
GO:MF carbon-oxygen lyase activity 78 1
KEGG Chemical carcinogenesis 101 1
KEGG Ovarian steroidogenesis 62 1
KEGG Metabolism of xenobiotics by cytochrome P450 73 1
KEGG Retinol metabolism 97 1
KEGG Tryptophan metabolism 51 1
KEGG Steroid hormone biosynthesis 91 1
REAC Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET) 7 1
REAC Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) 8 1
REAC Biosynthesis of protectins 3 1
REAC Biosynthesis of specialized proresolving mediators (SPMs) 17 1
REAC Biosynthesis of DHA-derived SPMs 16 1
REAC Xenobiotics 25 1
REAC RHO GTPases Activate WASPs and WAVEs 33 1
REAC Arachidonic acid metabolism 61 1
REAC Cytochrome P450 - arranged by substrate type 71 1
WP Fatty Acid Omega Oxidation 7 1
WP Estrogen metabolism 14 1
WP Oxidative Stress 28 1
WP Oxidation by Cytochrome P450 40 1
WP Tryptophan metabolism 44 1

2.2.13 Functional Enrichment - Liver-specific TCDD-AhR Regulated

kable(Diff_Liver_Interx_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size), 
      table.attr = "class=\"striped\"", format = "html")
source term_name term_size intersection_size
CORUM Parvulin-associated pre-rRNP complex 46 9
GO:BP cellular amide metabolic process 1077 55
GO:BP organonitrogen compound biosynthetic process 1570 65
GO:BP cellular metabolic process 10350 212
GO:BP small molecule metabolic process 1713 68
GO:BP organic acid metabolic process 944 48
GO:BP peptide metabolic process 835 45
GO:BP metabolic process 11429 224
GO:BP carboxylic acid metabolic process 896 45
GO:BP oxoacid metabolic process 908 45
GO:BP obsolete oxidation-reduction process 548 34
GO:BP peptide biosynthetic process 677 37
GO:BP organic substance metabolic process 10989 212
GO:BP amide biosynthetic process 793 40
GO:BP translation 657 36
GO:BP monocarboxylic acid metabolic process 616 34
GO:BP organic acid biosynthetic process 290 23
GO:BP catabolic process 2399 74
GO:BP primary metabolic process 10243 198
GO:BP organonitrogen compound metabolic process 6326 140
GO:BP organic substance catabolic process 1985 63
GO:BP carboxylic acid biosynthetic process 282 21
GO:BP cellular lipid metabolic process 994 41
GO:BP cellular catabolic process 2059 64
GO:BP small molecule biosynthetic process 617 31
GO:BP sulfur compound metabolic process 317 21
GO:BP lipid metabolic process 1344 47
GO:BP ribonucleoprotein complex biogenesis 413 23
GO:BP fatty acid metabolic process 425 23
GO:BP regulation of biological quality 3876 92
GO:BP biosynthetic process 5882 124
GO:BP cytoplasmic translation 101 11
GO:BP ribosome assembly 63 9
GO:BP organic substance biosynthetic process 5779 120
GO:BP ribosome biogenesis 288 17
GO:BP ribonucleoprotein complex assembly 182 13
GO:BP small molecule catabolic process 346 18
GO:BP ribonucleoprotein complex subunit organization 188 13
GO:BP cellular biosynthetic process 5715 116
GO:BP nitrogen compound metabolic process 9669 174
GO:BP benzene-containing compound metabolic process 30 6
GO:BP monocarboxylic acid biosynthetic process 194 13
GO:BP glutathione metabolic process 70 8
GO:BP cellular modified amino acid metabolic process 179 12
GO:BP organophosphate metabolic process 891 30
GO:BP fatty acid biosynthetic process 151 11
GO:BP NADP metabolic process 38 6
GO:BP unsaturated fatty acid metabolic process 133 10
GO:BP glycosyl compound metabolic process 86 8
GO:BP response to hormone 912 29
GO:BP response to toxic substance 240 13
GO:BP rRNA processing 208 12
GO:BP gland development 513 20
GO:BP cell redox homeostasis 29 5
GO:BP cellular lipid catabolic process 214 12
GO:BP ribosomal small subunit biogenesis 69 7
GO:BP protein metabolic process 5474 107
GO:BP mature ribosome assembly 6 3
GO:BP rRNA metabolic process 217 12
GO:BP carboxylic acid catabolic process 221 12
GO:BP organonitrogen compound catabolic process 1249 35
GO:BP toxin metabolic process 17 4
GO:BP carbohydrate metabolic process 587 21
GO:BP very long-chain fatty acid metabolic process 33 5
GO:BP monoacylglycerol catabolic process 7 3
GO:BP organic acid catabolic process 228 12
GO:BP ketone catabolic process 18 4
GO:BP positive regulation of cellular amide metabolic process 163 10
GO:BP nucleobase metabolic process 34 5
GO:BP regulation of angiogenesis 305 14
GO:BP homeostatic process 1922 47
GO:BP carbohydrate derivative metabolic process 975 29
GO:BP purine nucleobase metabolic process 19 4
GO:BP positive regulation of translation 135 9
GO:BP cellular protein metabolic process 4815 95
GO:BP blood vessel morphogenesis 647 22
GO:BP regulation of vasculature development 310 14
GO:BP alpha-amino acid catabolic process 80 7
GO:BP cellular detoxification 108 8
GO:BP cellular nitrogen compound metabolic process 6201 116
GO:BP androgen biosynthetic process 8 3
GO:BP ribosomal small subunit assembly 20 4
GO:BP regulation of cellular amide metabolic process 438 17
GO:BP liver development 173 10
GO:BP cellular aldehyde metabolic process 59 6
GO:BP hepaticobiliary system development 176 10
GO:BP response to insulin 284 13
GO:BP cellular response to toxic substance 115 8
GO:BP long-chain fatty acid metabolic process 115 8
GO:BP NADPH oxidation 9 3
GO:BP cellular process 17828 270
GO:BP response to xenobiotic stimulus 115 8
GO:BP nucleoside metabolic process 61 6
GO:BP nucleobase-containing small molecule metabolic process 537 19
GO:BP response to oxygen radical 22 4
GO:BP response to superoxide 22 4
GO:BP response to oxygen-containing compound 1820 44
GO:BP cellular response to chemical stimulus 3097 66
GO:BP angiogenesis 545 19
GO:BP localization 6168 114
GO:BP liver regeneration 42 5
GO:BP lipid catabolic process 335 14
GO:BP animal organ regeneration 91 7
GO:BP regulation of translation 377 15
GO:BP positive regulation of establishment of protein localization to telomere 10 3
GO:BP negative regulation of cell adhesion mediated by integrin 10 3
GO:BP cellular amino acid catabolic process 92 7
GO:BP membrane lipid metabolic process 187 10
GO:BP androgen metabolic process 24 4
GO:BP lipid biosynthetic process 647 21
GO:BP blood vessel development 743 23
GO:BP detoxification 123 8
GO:BP ribosomal large subunit biogenesis 69 6
GO:BP regulation of establishment of protein localization to telomere 11 3
GO:BP kynurenine metabolic process 11 3
GO:BP anatomical structure formation involved in morphogenesis 1165 31
GO:BP tube morphogenesis 911 26
GO:BP maturation of LSU-rRNA 27 4
GO:BP lactation 72 6
GO:BP regulation of establishment of protein localization to chromosome 12 3
GO:BP xenobiotic metabolic process 102 7
GO:BP vasculature development 773 23
GO:BP regulation of endocannabinoid signaling pathway 3 2
GO:BP response to oxidative stress 447 16
GO:BP positive regulation of DNA biosynthetic process 74 6
GO:BP icosanoid metabolic process 134 8
GO:BP ncRNA processing 363 14
GO:BP response to peptide hormone 452 16
GO:BP mammary gland development 170 9
GO:BP monoacylglycerol metabolic process 13 3
GO:BP positive regulation of protein localization to chromosome, telomeric region 13 3
GO:BP cellular response to xenobiotic stimulus 106 7
GO:BP response to drug 459 16
GO:BP prostanoid metabolic process 52 5
GO:BP prostaglandin metabolic process 52 5
GO:BP sphingolipid metabolic process 140 8
GO:BP cellular ketone metabolic process 213 10
GO:BP aldehyde catabolic process 14 3
GO:BP cellular amino acid metabolic process 253 11
GO:BP protein localization to organelle 859 24
GO:BP regulation of complement activation 15 3
GO:BP establishment of localization 4658 88
GO:BP xenobiotic catabolic process 15 3
GO:BP alpha-amino acid metabolic process 182 9
GO:BP regulation of protein localization to chromosome, telomeric region 15 3
GO:BP negative regulation of osteoblast differentiation 56 5
GO:BP nitrobenzene metabolic process 4 2
GO:BP glutathione derivative metabolic process 4 2
GO:BP negative regulation of endothelial cell chemotaxis 4 2
GO:BP L-kynurenine catabolic process 4 2
GO:BP cell death 2136 47
GO:BP glutathione derivative biosynthetic process 4 2
GO:BP cellular response to insulin stimulus 222 10
GO:BP establishment of protein localization to telomere 16 3
GO:BP nucleobase biosynthetic process 16 3
GO:BP response to organic substance 3418 68
GO:BP aromatic amino acid family catabolic process 16 3
GO:BP ribosomal subunit export from nucleus 16 3
GO:BP ribosome localization 16 3
GO:BP formation of cytoplasmic translation initiation complex 16 3
GO:BP tube development 1137 29
GO:BP response to peptide 531 17
GO:BP cytoplasmic translational initiation 35 4
GO:BP cellular response to peptide hormone stimulus 309 12
GO:BP cellular response to vascular endothelial growth factor stimulus 60 5
GO:BP rRNA-containing ribonucleoprotein complex export from nucleus 17 3
GO:BP glutamine family amino acid biosynthetic process 17 3
GO:BP translational initiation 121 7
GO:BP secondary metabolic process 61 5
GO:BP cellular amino acid biosynthetic process 62 5
GO:BP body fluid secretion 123 7
GO:BP ncRNA metabolic process 449 15
GO:BP alpha-amino acid biosynthetic process 62 5
GO:BP iron ion transport 63 5
GO:BP activation of membrane attack complex 5 2
GO:BP protein sulfation 5 2
GO:BP viral translational termination-reinitiation 5 2
GO:BP removal of superoxide radicals 18 3
GO:BP arginine biosynthetic process 5 2
GO:BP fatty acid beta-oxidation using acyl-CoA oxidase 5 2
GO:CC cytoplasm 11093 240
GO:CC intracellular anatomical structure 14111 260
GO:CC cytosolic ribosome 112 19
GO:CC ribosome 236 25
GO:CC cytosol 3849 110
GO:CC ribosomal subunit 200 23
GO:CC intracellular organelle 12510 232
GO:CC organelle 12827 233
GO:CC small ribosomal subunit 79 13
GO:CC intracellular membrane-bounded organelle 11363 212
GO:CC cytosolic small ribosomal subunit 45 10
GO:CC membrane-bounded organelle 11812 213
GO:CC ribonucleoprotein complex 725 32
GO:CC endomembrane system 4006 95
GO:CC endoplasmic reticulum 1761 53
GO:CC cytosolic large ribosomal subunit 64 9
GO:CC organelle membrane 3076 74
GO:CC mitochondrion 1827 51
GO:CC large ribosomal subunit 126 11
GO:CC organelle subcompartment 1580 45
GO:CC polysomal ribosome 32 6
GO:CC endoplasmic reticulum membrane 993 31
GO:CC endoplasmic reticulum subcompartment 999 31
GO:CC nuclear outer membrane-endoplasmic reticulum membrane network 1018 31
GO:CC polysome 70 7
GO:CC organelle envelope 1176 32
GO:CC envelope 1176 32
GO:CC mitochondrial envelope 736 23
GO:CC chaperonin-containing T-complex 10 3
GO:CC mitochondrial intermembrane space 99 7
GO:CC rough endoplasmic reticulum 105 7
GO:CC myelin sheath 206 10
GO:CC organelle envelope lumen 111 7
GO:CC eukaryotic 48S preinitiation complex 15 3
GO:CC COP9 signalosome 34 4
GO:CC eukaryotic translation initiation factor 3 complex 16 3
GO:CC synapse 1467 35
GO:CC eukaryotic 43S preinitiation complex 17 3
GO:CC translation preinitiation complex 18 3
GO:CC mitochondrial inner membrane 451 15
GO:CC membrane-enclosed lumen 4582 85
GO:CC organelle lumen 4582 85
GO:CC intracellular organelle lumen 4581 85
GO:CC cellular anatomical entity 19567 286
GO:CC mitochondrial membrane 677 19
GO:CC intracellular non-membrane-bounded organelle 4500 83
GO:CC preribosome 74 5
GO:CC non-membrane-bounded organelle 4515 83
GO:CC preribosome, large subunit precursor 24 3
GO:CC peroxisome 148 7
GO:CC microbody 148 7
GO:MF structural constituent of ribosome 172 21
GO:MF oxidoreductase activity 815 42
GO:MF rRNA binding 69 12
GO:MF catalytic activity 5665 128
GO:MF oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor 143 13
GO:MF oxidoreductase activity, acting on CH-OH group of donors 154 13
GO:MF flavin adenine dinucleotide binding 90 10
GO:MF structural molecule activity 612 25
GO:MF identical protein binding 2140 54
GO:MF anion binding 2420 58
GO:MF translation regulator activity 145 10
GO:MF RNA binding 1267 36
GO:MF oxidoreductase activity, acting on a sulfur group of donors 51 6
GO:MF small molecule binding 2543 59
GO:MF glutathione binding 17 4
GO:MF oligopeptide binding 17 4
GO:MF carbonyl reductase (NADPH) activity 7 3
GO:MF NADP binding 55 6
GO:MF lyase activity 198 11
GO:MF enzyme inhibitor activity 403 16
GO:MF ubiquitin ligase inhibitor activity 9 3
GO:MF oxidoreductase activity, acting on the CH-CH group of donors 60 6
GO:MF site-specific endodeoxyribonuclease activity, specific for altered base 2 2
GO:MF N,N-dimethylaniline monooxygenase activity 9 3
GO:MF amino acid binding 63 6
GO:MF ubiquitin-protein transferase inhibitor activity 10 3
GO:MF carboxylic ester hydrolase activity 153 9
GO:MF mRNA 5’-UTR binding 25 4
GO:MF ion binding 5862 109
GO:MF palmitoyl-CoA oxidase activity 3 2
GO:MF protein-disulfide reductase activity 27 4
GO:MF transition metal ion binding 1064 29
GO:MF 5.8S rRNA binding 3 2
GO:MF carbon-sulfur lyase activity 12 3
GO:MF nucleotide binding 2185 49
GO:MF nucleoside phosphate binding 2185 49
GO:MF acylglycerol lipase activity 13 3
GO:MF 5S rRNA binding 13 3
GO:MF steroid binding 114 7
GO:MF translation regulator activity, nucleic acid binding 113 7
GO:MF 3-hydroxy-arachidoyl-CoA dehydratase activity 4 2
GO:MF glutathione transferase activity 33 4
GO:MF 3-hydroxy-behenoyl-CoA dehydratase activity 4 2
GO:MF 3-hydroxy-lignoceroyl-CoA dehydratase activity 4 2
GO:MF very-long-chain 3-hydroxyacyl-CoA dehydratase activity 4 2
GO:MF disulfide oxidoreductase activity 34 4
GO:MF protein folding chaperone 35 4
GO:MF NAD binding 63 5
GO:MF oxidoreductase activity, acting on superoxide radicals as acceptor 5 2
GO:MF stearoyl-CoA 9-desaturase activity 5 2
GO:MF superoxide dismutase activity 5 2
GO:MF lipase activity 124 7
GO:MF organic cyclic compound binding 5768 104
GO:MF FAD binding 39 4
GO:MF transferase activity, transferring alkyl or aryl (other than methyl) groups 65 5
GO:MF translation factor activity, RNA binding 96 6
GO:MF complement binding 20 3
GO:MF acyl-CoA oxidase activity 6 2
GO:MF iron-sulfur cluster binding 71 5
GO:MF metal cluster binding 71 5
GO:MF metalloaminopeptidase activity 22 3
GO:MF protein homodimerization activity 676 19
GO:MF sulfur compound binding 256 10
GO:MF ubiquitin-protein transferase regulator activity 22 3
HP Abnormality of metabolism/homeostasis 2240 65
HP Abnormal mean corpuscular volume 45 6
HP Abnormal erythrocyte enzyme level 26 5
HP Visceromegaly 656 26
HP Reticulocytopenia 29 5
HP Abnormal circulating metabolite concentration 1099 37
HP Adenocarcinoma of the large intestine 26 5
HP Abnormal erythrocyte morphology 593 24
HP Abnormal enzyme/coenzyme activity 477 22
HP Persistence of hemoglobin F 25 5
HP Normochromic anemia 29 5
HP Abnormal circulating glutamine concentration 8 3
HP Abnormal hemoglobin 49 6
HP Duplication of thumb phalanx 49 6
HP Radial artery aplasia 18 4
HP Elevated red cell adenosine deaminase level 18 4
HP Hepatomegaly 504 21
HP Abnormal radial artery morphology 18 4
HP Adenocarcinoma of the intestines 31 5
HP Partial duplication of thumb phalanx 33 5
KEGG Ribosome 169 21
KEGG Coronavirus disease - COVID-19 241 22
KEGG Metabolic pathways 1563 63
KEGG Biosynthesis of unsaturated fatty acids 34 7
KEGG Fatty acid elongation 29 6
KEGG Drug metabolism - other enzymes 92 9
KEGG Drug metabolism - cytochrome P450 71 8
KEGG Metabolism of xenobiotics by cytochrome P450 73 8
KEGG Biosynthesis of amino acids 78 8
KEGG Glutathione metabolism 71 7
KEGG Chemical carcinogenesis 101 8
KEGG Biosynthesis of cofactors 154 10
KEGG Fatty acid metabolism 62 6
REAC Formation of a pool of free 40S subunits 98 20
REAC L13a-mediated translational silencing of Ceruloplasmin expression 108 20
REAC GTP hydrolysis and joining of the 60S ribosomal subunit 109 20
REAC Metabolism 1679 80
REAC Eukaryotic Translation Initiation 116 20
REAC Cap-dependent Translation Initiation 116 20
REAC SRP-dependent cotranslational protein targeting to membrane 89 17
REAC Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) 91 17
REAC Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 110 17
REAC Nonsense-Mediated Decay (NMD) 110 17
REAC Translation 217 23
REAC Formation of the ternary complex, and subsequently, the 43S complex 49 12
REAC Ribosomal scanning and start codon recognition 56 12
REAC Translation initiation complex formation 56 12
REAC Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S 57 12
REAC Major pathway of rRNA processing in the nucleolus and cytosol 167 18
REAC rRNA processing 167 18
REAC rRNA processing in the nucleus and cytosol 167 18
REAC Biological oxidations 204 17
REAC FMO oxidises nucleophiles 3 3
REAC Phase II - Conjugation of compounds 91 10
REAC Metabolism of lipids 573 28
REAC Glutathione conjugation 34 6
REAC Fatty acid metabolism 169 12
REAC Formation of the active cofactor, UDP-glucuronate 3 2
REAC alpha-linolenic (omega3) and linoleic (omega6) acid metabolism 12 3
REAC alpha-linolenic acid (ALA) metabolism 12 3
TF Factor: Kaiso; motif: SARNYCTCGCGAGAN; match class: 1 9949 200
TF Factor: E2F-1; motif: GNGGGCGGGRMN 14228 252
TF Factor: ZF5; motif: GSGCGCGR 14821 257
TF Factor: FOXN4; motif: NNWANNCGWMCGCGTCNNNNMT; match class: 1 12768 232
TF Factor: AhR; motif: NTNGCGTGNNN 3488 93
TF Factor: FOXN4; motif: NNWANNCGWMCGCGTCNNNNMT 16009 268
TF Factor: E2F-4; motif: NTTTCSCGCC 10545 201
TF Factor: ELK-1; motif: ACCGGAWRTN 14697 253
TF Factor: LKLF; motif: NGGGCGG 7220 152
TF Factor: CPBP; motif: NGGGCGG 7220 152
TF Factor: Sp3; motif: AGGGCGG 7220 152
TF Factor: SP6; motif: WGGGCGG 7220 152
TF Factor: ZF5; motif: NRNGNGCGCGCWN 14469 249
TF Factor: E2F; motif: GGCGSG 10391 195
TF Factor: ZF5; motif: NRNGNGCGCGCWN; match class: 1 11181 205
TF Factor: ZF5; motif: GSGCGCGR; match class: 1 12032 215
TF Factor: BEN; motif: CAGCGRNV; match class: 1 11980 214
TF Factor: AhR:Arnt; motif: KNNKNNTYGCGTGCMS 2875 76
TF Factor: Kaiso; motif: SARNYCTCGCGAGAN 13491 233
TF Factor: E2F-1; motif: GNGGGCGGGRMN; match class: 1 10601 195
TF Factor: Hes1; motif: NNCACGYGNN; match class: 1 11386 205
TF Factor: Elk-1; motif: NNNNCCGGAARTNN 10072 187
TF Factor: E2F-1; motif: NNNSSCGCSAANN 9013 172
TF Factor: Klf17; motif: NGGGCGG 6533 135
TF Factor: Hes1; motif: NNCACGYGNN 15504 255
TF Factor: AhR,; motif: NRCGTGNGN 4421 100
TF Factor: PEA3; motif: RCCGGAAGYN 9964 183
TF Factor: ZF5; motif: GYCGCGCARNGCNN 9484 176
TF Factor: AhR; motif: CCYCNRRSTNGCGTGASA 3480 82
TF Factor: E2F-4; motif: GNNGGCGGGAAN 5907 120
TF Factor: SP100; motif: NNCGTCGNNTAAWNN 8478 158
TF Factor: E2F; motif: NCSCGCSAAAN 5198 108
TF Factor: IRF6; motif: NNNACTCYCGGKNNN 13409 224
TF Factor: GABP-alpha; motif: CTTCCK 10764 189
TF Factor: AHR; motif: CACGCN; match class: 1 2729 66
TF Factor: E2F-7; motif: GRGGCGGGAANNN 7914 148
TF Factor: MYF6; motif: NNNRACAGNCNCNCC; match class: 1 7012 134
TF Factor: E2F; motif: TTTSGCGSG 5455 110
TF Factor: ELK-1; motif: ACCGGAWRTN; match class: 1 9029 163
TF Factor: LKLF; motif: NGGGCGG; match class: 1 2360 58
TF Factor: Sp3; motif: AGGGCGG; match class: 1 2360 58
TF Factor: SP6; motif: WGGGCGG; match class: 1 2360 58
TF Factor: CPBP; motif: NGGGCGG; match class: 1 2360 58
TF Factor: E2F1; motif: NNNNNGCGSSAAAN 5835 115
TF Factor: E2F-3; motif: GGCGGGN 11268 193
TF Factor: ZF5; motif: GYCGCGCARNGCNN; match class: 1 5819 114
TF Factor: TEL1; motif: CNCGGAANNN 10420 181
TF Factor: MYF6; motif: NNNRACAGNCNCNCC 14294 232
TF Factor: BEN; motif: CWGCGAYA 6569 125
TF Factor: IRF4; motif: NNNAYTCTCGGWNNN; match class: 1 8126 148
TF Factor: AhR:Arnt; motif: GRGKATYGCGTGMCWNSCC 5815 113
TF Factor: Egr-2; motif: GCGTGGGCGG 7210 134
TF Factor: AhR; motif: NTNGCGTGNNN; match class: 1 393 17
TF Factor: E2F-1; motif: TTTSGCGS 5974 115
TF Factor: BEN; motif: CAGCGRNV 16234 255
TF Factor: Pax-5; motif: RRMSWGANWYCTNRAGCGKRACSRYNSM 11986 201
TF Factor: c-Myc:Max; motif: GCCAYGYGSN; match class: 1 2409 57
TF Factor: p53; motif: RGRCWWGYCYNGRCWWGYYY 7799 142
TF Factor: Pax-3; motif: NNNNNNCGTCACGSTYNNNNN 12917 213
TF Factor: E2F-1; motif: NTTSGCGG; match class: 1 1815 46
TF Factor: RNF96; motif: BCCCGCRGCC 6337 120
TF Factor: ERG; motif: ACCGGAART 9550 166
TF Factor: HES-1; motif: GSCACGMGMC 3590 76
TF Factor: ZBED6; motif: NRRGCTCGCCNN 5544 107
TF Factor: AhR; motif: NNNKNGCGTGNSNNNNN 1222 34
TF Factor: SP4; motif: NNWAGGCGTGNCNNN 4923 97
TF Factor: Pax-5; motif: RRMSWGANWYCTNRAGCGKRACSRYNSM; match class: 1 5518 106
TF Factor: TEL1; motif: CNCGGAANNN; match class: 1 4384 88
TF Factor: E2F-1; motif: TTTSGCGCGMNR 5994 113
TF Factor: SP4; motif: NNKGGGCGKGNCN 1941 47
TF Factor: E2F; motif: NNTTTCGCGCN 5159 100
TF Factor: SP1:SP3; motif: CCSCCCCCYCC 6684 123
TF Factor: E2F; motif: NKCGCGCSAAAN 4858 95
TF Factor: Ets2; motif: ACCGGAWRYN 7919 141
TF Factor: E2F-4; motif: GCGGGAAANA 10318 175
TF Factor: NGFI-C; motif: WTGCGTGGGYGG 5000 97
TF Factor: BCL6B; motif: NNNNCCGCCCCWNNNN 13664 220
TF Factor: HIF-1alpha; motif: NCACGT 6382 118
TF Factor: CTCF; motif: NAGGGGGCGCNNKNNNN; match class: 1 9341 161
TF Factor: Tcfl5; motif: NNCNCGNGNN 6337 117
TF Factor: EGR-1; motif: TGCGTGGGCGK 4136 83
TF Factor: HIC1; motif: NNNGGKTGCCCSNNNNNN 2851 62
TF Factor: IRF4; motif: NNNAYTCTCGGWNNN 14544 231
TF Factor: Tcfl5; motif: NNCNCGNGNN; match class: 1 6337 117
TF Factor: c-ets-1; motif: ACCGGAWRYN 8408 147
TF Factor: E2F-4; motif: NGGGGGCGGGRMNN 6987 126
TF Factor: Egr-3; motif: NTGCGTGGGCGK 6055 112
TF Factor: AhR; motif: CCYCNRRSTNGCGTGASA; match class: 1 383 15
TF Factor: E2F-1; motif: TTTSGCGS; match class: 1 1582 39
TF Factor: arnt; motif: CACGYA 4582 89
TF Factor: HIF-1alpha; motif: GNACGTGM 6619 120
TF Factor: Zic1; motif: NNCCCCCGGGGGGG 9522 162
TF Factor: SP2; motif: GGGCGGGAC; match class: 1 3289 68
TF Factor: Elf-1; motif: AWCCCGGAAGTN 8375 145
TF Factor: E2F-1; motif: NNNSSCGCSAANN; match class: 1 4125 81
TF Factor: SP2; motif: GGGCGGGAC 8107 141
TF Factor: c-Ets-1; motif: NNNRCCGGAWRYNNNN 7309 129
TF Factor: Sp1; motif: GGNGGGGGNGGGGGMGGGGCNGGG 10752 178
TF Factor: ELF4; motif: CCCGGAARTN 7185 127
TF Factor: AP-2alpha; motif: NGCCYSNNGSN 6174 112
TF Factor: ZBED6; motif: NRRGCTCGCCNN; match class: 1 1364 34
TF Factor: Kid3; motif: CCACN; match class: 1 21165 303
TF Factor: Erm; motif: NCCGGAWGTN 5268 98
TF Factor: AP-2; motif: MKCCCSCNGGCG 8029 139
TF Factor: SP100; motif: NNCGTCGNNTAAWNN; match class: 1 3060 63
TF Factor: HES-1; motif: NNCKYGTGNNN 4062 79
TF Factor: CPBP; motif: SNCCCNN; match class: 1 19929 292
TF Factor: AP-2; motif: SNNNCCNCAGGCN 7085 125
TF Factor: E2F-4; motif: GCGGGAAANA; match class: 1 4700 89
TF Factor: GKLF; motif: GCCMCRCCCNNN 7840 136
TF Factor: Egr-2; motif: NTGCGTRGGCGK 5359 99
TF Factor: AP-2beta; motif: GCNNNGGSCNGVGGGN 5101 95
TF Factor: E2F-4; motif: NTTTCSCGCC; match class: 1 5364 99
TF Factor: GKLF; motif: WGGGYGKGGCCN 8978 152
TF Factor: Sp1; motif: NGGGGCGGGGN 9122 154
TF Factor: GKLF; motif: WGGGYGKGGCCN; match class: 1 3595 71
TF Factor: c-Myc:Max; motif: GCCAYGYGSN 7338 128
TF Factor: MAF; motif: GCTGAGTCAN 6937 122
TF Factor: GKLF; motif: NNNRGGNGNGGSN 15302 237
TF Factor: E2F-3; motif: GGCGGGN; match class: 1 6875 121
TF Factor: AHR; motif: CACGCN 8469 144
TF Factor: Zscan2; motif: GTCAAAACGC 59 5
TF Factor: WT1; motif: SMCNCCNSC 8128 139
TF Factor: AP-2gamma; motif: GCCYNCRGSN 7106 124
TF Factor: ER71; motif: ACCGGAARYN 4325 82
TF Factor: SAP-1a; motif: NRRCCGGAAGYRN 9134 153
TF Factor: Egr-2; motif: GCGTGGGCGG; match class: 1 2774 57
TF Factor: Pax-3; motif: NNNNNNCGTCACGSTYNNNNN; match class: 1 6178 110
TF Factor: ctcf; motif: CCNCNAGRKGGCRSTN 5575 101
TF Factor: Kaiso; motif: GCMGGGRGCRGS 11131 181
TF Factor: BTEB2; motif: RGGGNGKGGN 7600 131
TF Factor: IRF6; motif: NNNACTCYCGGKNNN; match class: 1 7128 124
TF Factor: GABPalpha_GABPbeta; motif: CTTCCKGY 2969 60
TF Factor: E2F; motif: TTTSGCGSG 4808 89
TF Factor: E2F-1; motif: NKTSSCGC 7904 135
TF Factor: E2F-1; motif: NKTSSCGC; match class: 1 2922 59
TF Factor: Pet-1; motif: GCNGGAAGYG 13321 210
TF Factor: LRH-1; motif: NYCAAGGYCAN; match class: 1 411 14
TF Factor: CTCF; motif: NAGGGGGCGCNNKNNNN 14310 223
TF Factor: WT1; motif: NGCGGGGGGGTSMMCYN 5297 96
WP Cytoplasmic Ribosomal Proteins 81 17
WP Omega-3/Omega-6 FA synthesis 15 4
WP Metapathway biotransformation 141 11
WP Translation Factors 49 6
WP Selenium Micronutrient Network 23 4
WP Folic Acid Network 23 4
WP Oxidative Stress and Redox Pathway 93 8

2.2.14 Functional Enrichment - Kidney-specific TCDD-AhR Regulated

kable(Diff_Kidney_Interx_PathwayEnrichment$result %>% dplyr::select(source, term_name, term_size, intersection_size), 
      table.attr = "class=\"striped\"", format = "html")
source term_name term_size intersection_size
GO:BP cellular response to decreased oxygen levels 156 3
GO:BP cellular response to oxygen levels 175 3
GO:BP cellular response to hypoxia 146 3
GO:BP regulation of B cell differentiation 30 2
GO:BP regulation of Wnt signaling pathway involved in dorsal/ventral axis specification 2 1
GO:BP epithelial cell proliferation 424 3
GO:BP reproductive structure development 503 3
GO:BP regulation of fibroblast proliferation 102 2
GO:BP negative regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation 1 1
GO:BP negative regulation of myeloid cell differentiation 97 2
GO:BP positive regulation of fat cell differentiation 67 2
GO:BP negative regulation of B cell differentiation 3 1
GO:BP stromal-epithelial cell signaling involved in prostate gland development 1 1
GO:BP cellular response to fibroblast growth factor stimulus 97 2
GO:BP canonical Wnt signaling pathway involved in regulation of type B pancreatic cell proliferation 2 1
GO:BP Wnt signaling pathway involved in dorsal/ventral axis specification 2 1
GO:BP cellular catabolic process 2059 5
GO:BP GDP-L-fucose salvage 1 1
GO:BP GDP-L-fucose biosynthetic process 3 1
GO:BP epidermal growth factor receptor signaling pathway via MAPK cascade 1 1
GO:BP response to decreased oxygen levels 341 3
GO:BP tube development 1137 4
GO:BP tube morphogenesis 911 4
GO:BP regulation of epithelial cell proliferation 359 3
GO:BP negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification 2 1
GO:BP reproductive system development 508 3
GO:BP response to oxygen levels 368 3
GO:BP negative regulation of planar cell polarity pathway involved in axis elongation 2 1
GO:BP regulation of planar cell polarity pathway involved in axis elongation 2 1
GO:BP positive regulation of aggrephagy 3 1
GO:BP regulation of aggrephagy 3 1
GO:BP regulation of morphogenesis of an epithelium 69 2
GO:BP positive regulation of intracellular mRNA localization 3 1
GO:BP regulation of intracellular mRNA localization 3 1
GO:BP phytanic acid metabolic process 1 1
GO:BP response to raffinose 1 1
GO:BP ERK1 and ERK2 cascade 344 3
GO:BP cellular response to raffinose 1 1
GO:BP positive regulation of canonical Wnt signaling pathway 106 2
GO:BP convergent extension involved in somitogenesis 1 1
GO:BP Wnt signaling pathway involved in somitogenesis 3 1
GO:BP circulatory system development 1174 4
GO:BP monocarboxylic acid catabolic process 122 2
GO:BP response to fibroblast growth factor 104 2
GO:BP lipid oxidation 120 2
GO:BP regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation 2 1
GO:BP cellular response to interleukin-1 103 2
GO:BP methyl-branched fatty acid metabolic process 3 1
GO:BP positive regulation of cellular catabolic process 414 3
GO:BP fibroblast proliferation 104 2
GO:BP response to organic cyclic compound 1043 4
GO:BP septum transversum development 2 1
GO:BP positive regulation of catabolic process 481 3
GO:BP proepicardium development 2 1
GO:BP response to abiotic stimulus 1177 4
GO:BP response to hypoxia 326 3
GO:BP fatty acid metabolic process 425 3
GO:BP MAPK cascade 771 4
GO:BP regulation of myeloid leukocyte differentiation 125 2
GO:BP neural crest cell fate commitment 3 1
GO:BP fatty acid catabolic process 99 2
GO:BP fatty acid oxidation 114 2
GO:BP phosphatidylinositol 3-kinase signaling 127 2
GO:BP response to interleukin-1 131 2
GO:BP positive regulation of Wnt signaling pathway 136 2
GO:BP cellular response to heparin 4 1
GO:BP GDP-L-fucose metabolic process 4 1
GO:BP axis elongation involved in somitogenesis 4 1
GO:BP regulation of fat cell differentiation 142 2
GO:BP canonical Wnt signaling pathway involved in regulation of cell proliferation 5 1
GO:BP positive regulation of hyaluronan biosynthetic process 5 1
GO:BP regulation of midbrain dopaminergic neuron differentiation 5 1
GO:BP response to organic substance 3418 6
GO:BP regulation of cell cycle process 599 3
GO:BP stem cell fate commitment 5 1
GO:BP nuclear-transcribed mRNA catabolic process, deadenylation-independent decay 5 1
GO:BP epithelial tube formation 151 2
GO:BP B cell differentiation 147 2
GO:BP response to heparin 5 1
GO:BP planar cell polarity pathway involved in axis elongation 5 1
GO:BP fatty acid beta-oxidation using acyl-CoA oxidase 5 1
GO:BP tube formation 163 2
GO:BP phosphatidylinositol-mediated signaling 162 2
GO:BP monocarboxylic acid metabolic process 616 3
GO:BP inositol lipid-mediated signaling 165 2
GO:BP prostate glandular acinus morphogenesis 6 1
GO:BP regulation of branching involved in prostate gland morphogenesis 6 1
GO:BP prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis 6 1
GO:BP negative regulation of non-canonical Wnt signaling pathway 6 1
GO:BP placenta development 172 2
GO:BP catabolic process 2399 5
GO:BP blood vessel morphogenesis 647 3
GO:BP positive regulation of developmental process 1412 4
GO:BP regulation of lymphocyte differentiation 178 2
GO:BP neural tube development 181 2
GO:BP regulation of keratinocyte apoptotic process 7 1
GO:BP regulation of multicellular organismal development 1444 4
GO:BP fatty acid alpha-oxidation 7 1
GO:BP keratinocyte apoptotic process 7 1
GO:BP chorio-allantoic fusion 8 1
GO:BP positive regulation of signal transduction 1506 4
GO:BP regulation of MAPK cascade 708 3
GO:BP positive regulation of epithelial tube formation 8 1
GO:BP regulation of epithelial tube formation 8 1
GO:BP regulation of dopaminergic neuron differentiation 8 1
GO:BP aggrephagy 8 1
GO:BP convergent extension involved in axis elongation 8 1
GO:BP cellular response to tumor necrosis factor 198 2
GO:BP negative regulation of fibroblast apoptotic process 10 1
GO:BP negative regulation of secretion 207 2
GO:BP carboxylic acid catabolic process 221 2
GO:BP convergent extension involved in gastrulation 10 1
GO:BP cellular response to steroid hormone stimulus 205 2
GO:BP positive regulation of fibroblast apoptotic process 9 1
GO:BP brain development 758 3
GO:BP myeloid leukocyte differentiation 219 2
GO:BP lipid modification 218 2
GO:BP positive regulation of epithelial cell proliferation 205 2
GO:BP regulation of cellular catabolic process 745 3
GO:BP positive regulation of monocyte differentiation 10 1
GO:BP positive regulation of protein localization to early endosome 9 1
GO:BP regulation of protein localization to early endosome 9 1
GO:BP protein kinase B signaling 214 2
GO:BP cellular lipid catabolic process 214 2
GO:BP blood vessel development 743 3
GO:BP regulation of hyaluronan biosynthetic process 9 1
GO:BP positive regulation of execution phase of apoptosis 10 1
GO:BP positive regulation of peroxisome proliferator activated receptor signaling pathway 9 1
GO:BP morphogenesis of a branching structure 220 2
GO:BP morphogenesis of a branching epithelium 203 2
GO:BP response to tumor necrosis factor 223 2
GO:BP regulation of myeloid cell differentiation 217 2
GO:BP positive regulation of cerebellar granule cell precursor proliferation 11 1
GO:BP vasculature development 773 3
GO:BP positive regulation of ERK1 and ERK2 cascade 225 2
GO:BP protein localization to early endosome 11 1
GO:BP prostate glandular acinus development 11 1
GO:BP bone trabecula formation 11 1
GO:BP organic acid catabolic process 228 2
GO:BP neural crest formation 11 1
GO:BP dorsal/ventral axis specification 11 1
GO:BP negative regulation of erythrocyte differentiation 11 1
GO:BP cellular response to transforming growth factor beta stimulus 231 2
GO:BP response to transforming growth factor beta 235 2
GO:BP mesendoderm development 11 1
GO:BP stress-activated MAPK cascade 231 2
GO:BP positive regulation of extrinsic apoptotic signaling pathway via death domain receptors 13 1
GO:BP midbrain dopaminergic neuron differentiation 14 1
GO:BP cellular response to cytokine stimulus 822 3
GO:BP positive regulation of protein localization to endosome 13 1
GO:BP cellular response to X-ray 12 1
GO:BP regulation of Wnt signaling pathway, planar cell polarity pathway 14 1
GO:BP intracellular mRNA localization 12 1
GO:BP regulation of protein localization to endosome 14 1
GO:BP planar cell polarity pathway involved in neural tube closure 12 1
GO:BP regulation of establishment of planar polarity involved in neural tube closure 13 1
GO:BP bone trabecula morphogenesis 14 1
GO:BP regulation of type B pancreatic cell proliferation 14 1
GO:BP establishment of planar polarity involved in neural tube closure 14 1
GO:BP positive regulation of non-canonical Wnt signaling pathway 14 1
GO:BP cellular response to salt stress 14 1
GO:BP regulation of cerebellar granule cell precursor proliferation 14 1
GO:BP negative regulation of platelet-derived growth factor receptor signaling pathway 13 1
GO:BP stress-activated protein kinase signaling cascade 246 2
GO:BP intracellular receptor signaling pathway 244 2
GO:BP head development 805 3
GO:BP regulation of B cell activation 248 2
GO:BP branching involved in prostate gland morphogenesis 13 1
GO:BP hyaluronan biosynthetic process 14 1
GO:BP nucleotide salvage 14 1
GO:BP small molecule metabolic process 1713 4
GO:BP positive regulation of cell communication 1725 4
GO:BP fat cell differentiation 247 2
GO:BP cellular potassium ion homeostasis 13 1
GO:BP positive regulation of signaling 1732 4
GO:BP establishment or maintenance of transmembrane electrochemical gradient 12 1
GO:BP regulation of canonical Wnt signaling pathway 241 2
GO:BP positive regulation of epidermal growth factor-activated receptor activity 13 1
GO:BP sodium ion export across plasma membrane 14 1
GO:BP regulation of cell population proliferation 1753 4
GO:BP regulation of cellular localization 867 3
GO:BP regulation of peptidyl-tyrosine phosphorylation 267 2
GO:BP establishment of planar polarity of embryonic epithelium 16 1
GO:BP carboxylic acid metabolic process 896 3
GO:BP oxoacid metabolic process 908 3
GO:BP negative regulation of JUN kinase activity 15 1
GO:BP mesenchyme development 280 2
GO:BP negative regulation of osteoblast proliferation 16 1
GO:BP positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay 16 1
GO:BP convergent extension 16 1
GO:BP 3’-UTR-mediated mRNA destabilization 16 1
GO:BP export from cell 908 3
GO:BP regulation of cell cycle 898 3
GO:BP cellular response to prostaglandin E stimulus 15 1
GO:BP cellular response to stress 1805 4
GO:BP regulation of peroxisome proliferator activated receptor signaling pathway 16 1
GO:BP nucleotide-sugar biosynthetic process 16 1
GO:BP regulation of catabolic process 893 3
GO:BP regulation of protein secretion 292 2
GO:BP regulation of MAP kinase activity 288 2
GO:BP regulation of leukocyte differentiation 292 2
GO:BP negative regulation of androgen receptor signaling pathway 17 1
GO:BP regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay 17 1
GO:BP enzyme linked receptor protein signaling pathway 916 3
GO:BP negative regulation of cholesterol efflux 17 1
GO:BP canonical Wnt signaling pathway 290 2
GO:BP negative regulation of cell migration 289 2
GO:BP cell migration involved in heart development 17 1
GO:BP regulation of monocyte differentiation 18 1
GO:BP protein localization to peroxisome 18 1
GO:BP negative regulation of nitric oxide biosynthetic process 18 1
GO:BP spongiotrophoblast layer development 18 1
GO:BP regulation of cell migration 934 3
GO:BP response to cytokine 935 3
GO:BP organic acid metabolic process 944 3
GO:BP cellular response to estrogen stimulus 18 1
GO:BP negative regulation of nitric oxide metabolic process 18 1
GO:BP regulation of Wnt signaling pathway 302 2
GO:BP protein targeting to peroxisome 18 1
GO:BP establishment of protein localization to peroxisome 18 1
GO:BP negative regulation of cell motility 303 2
GO:BP cell proliferation in external granule layer 19 1
GO:BP regulation of endocytic recycling 19 1
GO:BP regulation of anatomical structure morphogenesis 963 3
GO:BP regulation of execution phase of apoptosis 19 1
GO:BP transport 4502 6
GO:BP cerebellar granule cell precursor proliferation 19 1
GO:BP cellular response to environmental stimulus 313 2
GO:BP negative regulation of cellular component movement 313 2
GO:BP cellular response to abiotic stimulus 313 2
GO:BP tissue development 1923 4
GO:BP cell proliferation in hindbrain 20 1
GO:BP cellular response to prostaglandin stimulus 20 1
GO:BP negative regulation of bone remodeling 20 1
GO:BP regulation of cell motility 986 3
GO:BP regulation of ERK1 and ERK2 cascade 325 2
GO:BP mammary gland alveolus development 21 1
GO:BP cellular sodium ion homeostasis 21 1
GO:BP peroxisomal transport 21 1
GO:BP cellular lipid metabolic process 994 3
GO:BP mammary gland lobule development 21 1
GO:BP peroxisome proliferator activated receptor signaling pathway 22 1
GO:BP lipid catabolic process 335 2
GO:BP regulation of fibroblast apoptotic process 22 1
GO:BP nitrogen compound transport 1986 4
GO:BP organic substance catabolic process 1985 4
GO:BP cellular response to vitamin D 22 1
GO:BP negative regulation of locomotion 336 2
GO:BP central nervous system development 1023 3
GO:BP establishment of localization 4658 6
GO:MF prostaglandin-I synthase activity 1 1
GO:MF pristanoyl-CoA oxidase activity 1 1
GO:MF fucokinase activity 1 1
GO:MF P-type potassium:proton transporter activity 3 1
GO:MF thiamine pyrophosphate binding 8 1
GO:MF lyase activity 198 2
GO:MF oxidoreductase activity, acting on the CH-CH group of donors, oxygen as acceptor 9 1
GO:MF P-type sodium transporter activity 9 1
GO:MF P-type sodium:potassium-exchanging transporter activity 9 1
GO:MF hydroperoxy icosatetraenoate dehydratase activity 7 1
GO:MF acyl-CoA oxidase activity 6 1
REAC Peroxisomal lipid metabolism 27 2
REAC Fatty acid metabolism 169 3
REAC Sterols are 12-hydroxylated by CYP8B1 1 1
REAC Peroxisomal protein import 61 2
WP Eicosanoid metabolism via Cyclo Oxygenases (COX) 31 2